M. Furuya, J. Kikuta, S. Fujimori, S. Seno, H. Maeda et al., Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo, Nat Commun, vol.9, p.300, 2018.

N. A. Sims and T. J. Martin, Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit, BoneKEy Rep, vol.3, p.481, 2014.

D. T. Graves, J. Li, and D. L. Cochran, Inflammation and uncoupling as mechanisms of periodontal bone loss, J Dental Res, vol.90, pp.143-53, 2011.

H. Takayanagi, Inflammatory bone destruction and osteoimmunology, J Periodontal Res, vol.40, pp.287-93, 2005.

T. Nakashima, M. Hayashi, T. Fukunaga, K. Kurata, M. Oh-hora et al., Evidence for osteocyte regulation of bone homeostasis through RANKL expression, Nat Med, vol.17, pp.1231-1235, 2011.

J. Xiong, M. Onal, R. L. Jilka, R. S. Weinstein, S. C. Manolagas et al., Matrixembedded cells control osteoclast formation, Nat Med, vol.17, pp.1235-1276, 2011.

Y. Ikebuchi, S. Aoki, M. Honma, M. Hayashi, Y. Sugamori et al., Coupling of bone resorption and formation by RANKL reverse signalling, Nature, vol.561, pp.195-200, 2018.

T. Kawai, T. Matsuyama, Y. Hosokawa, S. Makihira, M. Seki et al., B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease, Am J Pathol, vol.169, pp.987-98, 2006.

M. Tsukasaki, N. Komatsu, K. Nagashima, T. Nitta, W. Pluemsakunthai et al., Host defense against oral microbiota by bone-damaging T cells, Nat Commun, vol.9, p.701, 2018.

Y. Takei, T. Minamizaki, and Y. Y. , Functional diversity of fibroblast growth factors in bone formation, Int J Endocrinol, p.729352, 2015.

O. G. Davies, L. M. Grover, M. P. Lewis, and Y. Liu, PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification, J Tissue Eng Regenerat Med, vol.12, pp.355-67, 2018.

S. Yakar, C. J. Rosen, W. G. Beamer, C. L. Ackert-bicknell, Y. Wu et al., Circulating levels of IGF-1 directly regulate bone growth and density, J Clin Invest, vol.110, pp.771-81, 2002.

M. Wu, G. Chen, and Y. Li, TGF-? and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease, Bone Res, vol.4, p.16009, 2016.

Y. Chen and B. A. Alman, Wnt pathway, an essential role in bone regeneration, J Cell Biochem, vol.106, pp.353-62, 2009.

X. Tu, J. Delgado-calle, K. W. Condon, M. Maycas, H. Zhang et al., Osteocytes mediate the anabolic actions of canonical Wnt/betacatenin signaling in bone, Proc Natl Acad Sci, vol.112, pp.478-86, 2015.

M. Phimphilai, Z. Zhao, H. Boules, H. Roca, and R. T. Franceschi, BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype, J Bone Mineral Res, vol.21, pp.637-683, 2006.

B. Ruaro, A. Casabella, S. Paolino, C. Pizzorni, M. Ghio et al., Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS), Clin Rheumatol, vol.37, pp.3057-62, 2018.

M. H. Napimoga, C. Nametala, F. L. Da-silva, T. S. Miranda, J. P. Bossonaro et al., Involvement of the Wnt-beta-catenin signalling antagonists, sclerostin and dickkopf-related protein 1, in chronic periodontitis, J Clin Periodontol, vol.41, pp.550-557, 2014.

M. M. Matzelle, M. A. Gallant, K. W. Condon, N. C. Walsh, C. A. Manning et al., Resolution of inflammation induces osteoblast function and regulates the Wnt signaling pathway, Arthritis Rheumat, vol.64, pp.1540-50, 2012.

D. A. Glass, . Ii, P. Bialek, J. D. Ahn, M. Starbuck et al., Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation, Dev Cell, vol.8, pp.751-64, 2005.

G. Hajishengallis, Periodontitis: from microbial immune subversion to systemic inflammation, Nat Rev Immunol, vol.15, pp.30-44, 2015.

G. Hajishengallis and J. M. Korostoff, Revisiting the Page & Schroeder model: the good, the bad and the unknowns in the periodontal host response 40 years later, Periodontology, vol.75, pp.116-51, 2000.

P. N. Papapanou, M. Sanz, N. Buduneli, T. Dietrich, M. Feres et al., Periodontitis: Consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions, J Periodontol, vol.45, pp.162-70, 2018.

S. Kurgan and A. Kantarci, Molecular basis for immunohistochemical and inflammatory changes during progression of gingivitis to periodontitis, Periodontology 2000, vol.76, pp.51-67, 2018.

G. Hajishengallis, The inflammophilic character of the periodontitisassociated microbiota, Mol Oral Microbiol, vol.29, pp.248-57, 2014.

G. Hajishengallis, Complement and periodontitis, Biochem Pharmacol, vol.80, pp.1992-2001, 2010.

H. A. Schenkein and R. J. Genco, Gingival fluid and serum in periodontal diseases. II. Evidence for cleavage of complement components C3, C3 proactivator (factor B) and C4 in gingival fluid, J Periodontol, vol.48, pp.778-84, 1977.

G. Hajishengallis, E. Hajishengallis, T. Kajikawa, B. Wang, D. Yancopoulou et al., Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application, Semi Immunol, vol.28, pp.285-91, 2016.

S. Liang, J. L. Krauss, H. Domon, M. L. Mcintosh, K. B. Hosur et al., The C5a receptor impairs IL-12-dependent clearance of Porphyromonas gingivalis and is required for induction of periodontal bone loss, J Immunol, vol.186, pp.869-77, 2011.

E. P. Grant, D. Picarella, T. Burwell, T. Delaney, A. Croci et al., Essential role for the C5a receptor in regulating the effector phase of synovial infiltration and joint destruction in experimental arthritis, J Exp Med, vol.196, pp.1461-71, 2002.

Y. Modinger, B. Loffler, M. Huber-lang, and I. A. , Complement involvement in bone homeostasis and bone disorders, Sem Immunol, vol.37, pp.53-65, 2018.

I. Olsen, J. D. Lambris, and G. Hajishengallis, Porphyromonas gingivalis disturbs host-commensal homeostasis by changing complement function, J Oral Microbiol, vol.9, p.1340085, 2017.

E. Hajishengallis and G. Hajishengallis, Neutrophil homeostasis and periodontal health in children and adults, J Dental Res, vol.93, pp.231-238, 2014.

G. Hajishengallis, N. M. Moutsopoulos, E. Hajishengallis, and T. Chavakis, Immune and regulatory functions of neutrophils in inflammatory bone loss, Semi Immunol, vol.28, pp.146-58, 2016.

N. M. Moutsopoulos, J. Konkel, M. Sarmadi, M. A. Eskan, T. Wild et al., Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss, Sci Transl Med, vol.6, pp.229-269, 2014.

M. Sochalska and J. Potempa, Manipulation of neutrophils by Porphyromonas gingivalis in the development of periodontitis. Front Cell Infect Microbiol, vol.7, p.197, 2017.

T. Maekawa, J. L. Krauss, T. Abe, R. Jotwani, M. Triantafilou et al., Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis, Cell Host Microbe, vol.15, pp.768-78, 2014.

M. R. Ling, I. L. Chapple, and J. B. Matthews, Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis, Innate Immunity, vol.21, pp.714-739, 2015.

A. Kantarci, K. Oyaizu, and T. E. Van-dyke, Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis, J Periodontol, vol.74, pp.66-75, 2003.

I. Allaeys, D. Rusu, S. Picard, M. Pouliot, P. Borgeat et al., Osteoblast retraction induced by adherent neutrophils promotes osteoclast bone resorption: implication for altered bone remodeling in chronic gout, Lab Invest, vol.91, pp.905-925, 2011.

N. Zhang, B. Schroppel, G. Lal, C. Jakubzick, X. Mao et al., Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response, Immunity, vol.30, pp.458-69, 2009.

N. Lewkowicz, M. P. Mycko, P. Przygodzka, H. ?wikli?ska, M. Cichalewska et al., Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10, Mucosal Immunol, vol.9, p.364, 2015.

N. Dutzan, J. E. Konkel, T. Greenwell-wild, and N. M. Moutsopoulos, Characterization of the human immune cell network at the gingival barrier, Mucosal Immunol, vol.9, pp.1163-72, 2016.

H. Hasturk, A. Kantarci, and T. E. Van-dyke, Oral inflammatory diseases and systemic inflammation: role of the macrophage, Front Immunol, vol.3, p.118, 2012.

Y. Lavin, A. Mortha, A. Rahman, and M. Merad, Regulation of macrophage development and function in peripheral tissues, Nat Rev Immunol, vol.15, pp.731-775, 2015.

P. J. Murray and T. A. Wynn, Protective and pathogenic functions of macrophage subsets, Nat Rev Immunol, vol.11, pp.723-760, 2011.

C. Sima and M. Glogauer, Macrophage subsets and osteoimmunology: tuning of the immunological recognition and effector systems that maintain alveolar bone, Periodontology, vol.63, pp.80-101, 2000.

J. Yang, Y. Zhu, D. Duan, P. Wang, Y. Xin et al., Enhanced activity of macrophage M1/M2 phenotypes in periodontitis, Arch Oral Biol, vol.96, pp.234-276, 2018.

T. Yu, L. Zhao, X. Huang, C. Ma, Y. Wang et al., Enhanced activity of the macrophage M1/M2 phenotypes and phenotypic switch to M1 in periodontal infection, J Periodontol, vol.87, pp.1092-102, 2016.

S. Miyajima, K. Naruse, Y. Kobayashi, N. Nakamura, T. Nishikawa et al., Periodontitis-activated monocytes/macrophages cause aortic inflammation, Sci Rep, vol.4, p.5171, 2014.

A. Viniegra, H. Goldberg, C. Cil, N. Fine, Z. Sheikh et al., Resolving macrophages counter osteolysis by anabolic actions on bone cells, J Dental Res, vol.97, pp.1160-1169, 2018.

P. J. Baker, M. Dixon, R. T. Evans, L. Dufour, J. E. Roopenian et al., CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice, Infect Immunity, vol.67, pp.2804-2813, 1999.

E. M. Cardoso and F. A. Arosa, CD8(+) T cells in chronic periodontitis: roles and rules. Front Immunol, vol.8, p.145, 2017.

J. A. Bluestone, C. R. Mackay, O. Shea, J. J. Stockinger, and B. , The functional plasticity of T cell subsets, Nat Rev Immunol, vol.9, p.811, 2009.

G. P. Garlet and W. V. Giannobile, Macrophages: the bridge between inflammation resolution and tissue repair?, J Dental Res, vol.97, pp.1079-81, 2018.

J. Diaz-zuniga, S. Melgar-rodriguez, L. Rojas, C. Alvarez, G. Monasterio et al., Increased levels of the T-helper 22-associated cytokine (interleukin-22) and transcription factor (aryl hydrocarbon receptor) in patients with periodontitis are associated with osteoclast resorptive activity and severity of the disease, J Periodontal Res, vol.52, pp.893-902, 2017.

J. Diaz-zuniga, S. Melgar-rodriguez, G. Monasterio, M. Pujol, L. Rojas et al., Differential human Th22-lymphocyte response triggered by Aggregatibacter actinomycetemcomitans serotypes, Arch Oral Biol, vol.78, pp.26-33, 2017.

G. P. Garlet, C. R. Cardoso, A. P. Campanelli, T. P. Garlet, M. J. Avila-campos et al., The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice, vol.10, pp.489-96, 2008.

G. Mizraji, M. Nassar, H. Segev, H. Sharawi, E. -. Berchoer et al., Porphyromonas gingivalis promotes unrestrained Type I interferon production by dysregulating TAM signaling via MYD88 degradation, Cell Rep, vol.18, pp.419-450, 2017.

X. O. Yang, B. P. Pappu, R. Nurieva, A. Akimzhanov, H. S. Kang et al., T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma, Immunity, vol.28, pp.29-39, 2008.

N. Dutzan, L. Abusleme, H. Bridgeman, T. Greenwell-wild, T. Zangerle-murray et al., On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity, vol.46, pp.133-180, 2017.

N. Dutzan, T. Kajikawa, L. Abusleme, T. Greenwell-wild, C. E. Zuazo et al., A dysbiotic microbiome triggers Th17 cells to mediate oral mucosal immunopathology in mice and humans, Sci Transl Med, vol.10, p.797, 2018.

A. C. Araujo-pires, A. E. Vieira, C. F. Francisconi, C. C. Biguetti, A. Glowacki et al., IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis, J Bone Mineral Res, vol.30, pp.412-434, 2015.

C. Alvarez, C. Rojas, L. Rojas, E. A. Cafferata, G. Monasterio et al., Regulatory T lymphocytes in periodontitis: a translational view, Medi Inflamm, p.7806912, 2018.

T. Abe, M. Alsarhan, M. R. Benakanakere, T. Maekawa, D. F. Kinane et al., The B cell-stimulatory cytokines BLyS and APRIL are elevated in human periodontitis and are required for B cell-dependent bone loss in experimental murine periodontitis, J Immunol, vol.195, pp.1427-1462, 2015.

T. Nakajima, R. Amanuma, K. Ueki-maruyama, O. T. Honda, T. Ito et al., CXCL13 expression and follicular dendritic cells in relation to B-cell infiltration in periodontal disease tissues, J Periodontal Res, vol.43, pp.635-676, 2008.

J. Demoersman, P. Pochard, C. Framery, Q. Simon, S. Boisrame et al., B cell subset distribution is altered in patients with severe periodontitis, PLoS ONE, vol.13, p.192986, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01727766

R. Mahanonda, C. Champaiboon, K. Subbalekha, N. Sa-ard-iam, W. Rattanathammatada et al., Human memory B cells in healthy gingiva, gingivitis, and periodontitis, J Immunol, vol.197, pp.715-740, 2016.

C. Rosser-elizabeth and C. Mauri, Regulatory B cells: origin, phenotype, and function, Immunity, vol.42, pp.607-619, 2015.

Y. Wang, X. Yu, J. Lin, Y. Hu, Q. Zhao et al., B10 cells alleviate periodontal bone loss in experimental periodontitis, Infect Immunity, vol.85, pp.335-352, 2017.

G. Jonasson, I. Skoglund, and M. Rythen, The rise and fall of the alveolar process: dependency of teeth and metabolic aspects, Arch Oral Biol, vol.96, pp.195-200, 2018.

S. Pacios, W. Xiao, M. Mattos, J. Lim, R. S. Tarapore et al., Osteoblast lineage cells play an essential role in periodontal bone loss through activation of nuclear factor-kappa B. Sci Rep, vol.5, p.16694, 2015.

Q. Wu, X. Zhou, D. Huang, Y. Ji, and F. Kang, IL-6 enhances osteocyte-mediated osteoclastogenesis by promoting JAK2 and RANKL activity in vitro, Cell Physiol Biochem, vol.41, pp.1360-1369, 2017.

J. Li, M. Yu, A. M. Tyagi, C. Vaccaro, E. Hsu et al., IL-17 receptor signaling in osteoblasts/osteocytes mediates PTH-induced bone loss and enhances osteocytic RANKL production, J Bone Mineral Res, vol.34, pp.349-60, 2019.

D. T. Graves, A. Alshabab, M. L. Albiero, M. Mattos, J. D. Corrêa et al., Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL, J Clin Periodontol, vol.45, pp.285-92, 2018.

E. Sakamoto, J. Kido, R. Takagi, Y. Inagaki, K. Naruishi et al., Advanced glycation end-product 2 and Porphyromonas gingivalis lipopolysaccharide increase sclerostin expression in mouse osteocyte-like cells, Bone, vol.122, pp.22-30, 2019.

D. Lin, L. Li, Y. Sun, W. Wang, X. Wang et al., IL-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1-JNK/NF-?B pathways, Immunology, vol.144, pp.472-85, 2014.

Y. Alippe, C. Wang, B. Ricci, J. Xiao, C. Qu et al., Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation. Sci Rep, vol.7, p.6630, 2017.

S. Wei, H. Kitaura, P. Zhou, F. P. Ross, and S. L. Teitelbaum, IL-1 mediates TNF-induced osteoclastogenesis, J Clin Invest, vol.115, pp.282-90, 2005.

T. Kajikawa, R. A. Briones, R. Resuello, J. V. Tuplano, E. S. Reis et al., Safety and efficacy of the complement inhibitor AMY-101 in a natural model of periodontitis in non-human primates, Mol Therapy Methods Clin Dev, vol.6, pp.207-222, 2017.

T. Maekawa, R. A. Briones, R. R. Resuello, J. V. Tuplano, E. Hajishengallis et al., Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3, J Clin Periodontol, vol.43, pp.238-287, 2016.

Z. Zhuang, S. Yoshizawa-smith, A. Glowacki, K. Maltos, C. Pacheco et al., Induction of M2 macrophages prevents bone loss in murine periodontitis models, J Dental Res, vol.98, pp.200-208, 2018.

Y. Jin, L. Wang, D. Liu, and X. Lin, Tamibarotene modulates the local immune response in experimental periodontitis, Int Immunopharmacol, vol.23, pp.537-582, 2014.

L. Wang, J. Wang, Y. Jin, H. Gao, and X. Lin, Oral administration of all-trans retinoic acid suppresses experimental periodontitis by modulating the Th17/treg imbalance, J Periodontol, vol.85, pp.740-50, 2014.

G. Mizraji, O. Heyman, T. E. Van-dyke, and A. Wilensky, Resolvin D2 restrains Th1 immunity and prevents alveolar bone loss in murine periodontitis, Front Immunol, vol.9, p.785, 2018.

Y. Hu, P. Yu, X. Yu, X. Hu, T. Kawai et al., IL-21/anti-Tim1/CD40 ligand promotes B10 activity in vitro and alleviates bone loss in experimental periodontitis in vivo. Biochim et Biophy Acta Mol Basis Dis, vol.1863, pp.2149-57, 2017.

F. Cavalla, A. C. Araujo-pires, C. C. Biguetti, and G. P. Garlet, Cytokine networks regulating inflammation and immune defense in the oral cavity. Curr Oral Health Rep, vol.1, pp.104-117, 2014.

F. Cavalla, C. C. Biguetti, T. Garlet, A. Trombone, and G. P. Garlet, Inflammatory Pathways of Bone Resorption in Periodontitis, Pathogenesis of Periodontal Diseases Biological Concepts for Clinicians, pp.59-86, 2018.

C. F. Francisconi, A. E. Vieira, C. C. Biguetti, A. J. Glowacki, A. P. Trombone et al., Characterization of the protective role of regulatory T cells in experimental periapical lesion development and their chemoattraction manipulation as a therapeutic tool, J Endodont, vol.42, pp.120-126, 2016.

G. P. Garlet, Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints, J Dental Res, vol.89, pp.1349-63, 2010.

L. Jansson, Relationship between apical periodontitis and marginal bone loss at individual level from a general population, Int Dental J, vol.65, pp.71-77, 2015.

N. Silva, L. Abusleme, D. Bravo, N. Dutzan, J. Garcia-sesnich et al., Host response mechanisms in periodontal diseases, J Appl Oral Sci, vol.23, pp.329-55, 2015.

C. E. Repeke, S. B. Ferreira, A. E. Vieira, E. M. Silveira, M. J. Avila-campos et al., Dose-response met-RANTES treatment of experimental periodontitis: a narrow edge between the disease severity attenuation and infection control, PLoS ONE, vol.6, 2011.

P. L. Tomson and S. R. Simon, Contemporary cleaning and shaping of the root canal system, Primary Dental J, vol.5, pp.46-53, 2016.

J. Darcey, R. V. Roudsari, S. Jawad, C. Taylor, and M. Hunter, Modern endodontic principles, vol.43, pp.114-120, 2016.

R. Menezes-silva, S. Khaliq, K. Deeley, A. Letra, and A. R. Vieira, Genetic susceptibility to periapical disease: conditional contribution of MMP2 and MMP3 genes to the development of periapical lesions and healing response, J Endodont, vol.38, pp.604-611, 2012.

M. Hernandez, N. Dutzan, J. Garcia-sesnich, L. Abusleme, A. Dezerega et al., Host-pathogen interactions in progressive chronic periodontitis, J Dental Res, vol.90, 2011.

J. C. Provenzano, H. S. Antunes, F. R. Alves, I. N. Rocas, W. S. Alves et al., Host-bacterial interactions in post-treatment apical periodontitis: a metaproteome analysis, J Endodont, vol.42, pp.880-885, 2016.

G. P. Garlet, A. P. Trombone, R. Menezes, A. Letra, C. E. Repeke et al., The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies: a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition, J Clin Periodontol, vol.39, pp.323-355, 2012.

A. Dill, A. Letra, L. Chaves-de-souza, M. Yadlapati, C. C. Biguetti et al., Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development, J Endodont, vol.41, pp.197-200, 2015.

K. Maheshwari, R. M. Silva, L. Guajardo-morales, G. P. Garlet, A. R. Vieira et al., Heat shock 70 protein genes and genetic susceptibility to apical periodontitis, J Endodont, vol.42, pp.1467-71, 2016.

F. Cavalla, C. C. Biguetti, T. J. Dionisio, M. Azevedo, W. Martins et al., CCR5Delta32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes, Cytokine, vol.103, pp.142-151, 2018.

F. Cavalla, P. Hernández-ríos, T. Sorsa, C. Biguetti, and M. Hernández, Matrix metalloproteinases as regulators of periodontal inflammation, Int J Mol Sci, vol.18, p.440, 2017.

A. P. Trombone, F. Cavalla, E. M. Silveira, C. B. Andreo, C. F. Francisconi et al., MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements, J Appl Oral Sci, vol.24, pp.366-75, 2016.

U. H. Lerner and C. Ohlsson, The WNT system: background and its role in bone, J Int Med, vol.277, pp.630-679, 2015.

Z. Tan, N. Ding, H. Lu, J. A. Kessler, and L. Kan, Wnt signaling in physiological and pathological bone formation, Histol Histopathol, vol.34, p.18062, 2018.

R. Menezes, T. P. Garlet, A. Letra, C. M. Bramante, A. P. Campanelli et al., Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: possible association with progressive or stable nature of the lesions, J Endodont, vol.34, pp.932-940, 2008.

A. C. Araujo-pires, C. F. Francisconi, C. C. Biguetti, F. Cavalla, A. M. Aranha et al., Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status, J Appl Oral Sci, vol.22, pp.336-382, 2014.

X. Hu and L. B. Ivashkiv, Cross-regulation of signaling pathways by interferongamma: implications for immune responses and autoimmune diseases, Immunity, vol.31, pp.539-50, 2009.

J. P. Van-hamburg and S. W. Tas, Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis, J Autoimmunity, vol.87, pp.69-81, 2018.

L. Wang, Y. Zhao, and S. Shi, Interplay between mesenchymal stem cells and lymphocytes: implications for immunotherapy and tissue regeneration, J Dental Res, vol.91, pp.1003-1013, 2012.

C. F. Francisconi, A. E. Vieira, M. Azevedo, A. P. Tabanez, A. C. Fonseca et al., RANKL triggers treg-mediated immunoregulation in inflammatory osteolysis, J Dental Res, vol.97, pp.917-944, 2018.

J. Lin, L. Yang, H. M. Silva, A. Trzeciak, Y. Choi et al., Increased generation of Foxp3(+) regulatory T cells by manipulating antigen presentation in the thymus, Nat Commun, vol.7, p.10562, 2016.

F. Cavalla, M. Reyes, R. Vernal, C. Alvarez, R. Paredes et al., High levels of CXC ligand 12/stromal cell-derived factor 1 in apical lesions of endodontic origin associated with mast cell infiltration, J Endodont, vol.39, pp.1234-1243, 2013.

F. Rivellese, D. Mauro, A. Nerviani, S. Pagani, L. Fossati-jimack et al., Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production, Ann Rheumat Dis, vol.77, pp.1773-81, 2018.

C. Cardamone, R. Parente, G. D. Feo, and M. Triggiani, Mast cells as effector cells of innate immunity and regulators of adaptive immunity, Immunol Lett, vol.178, pp.10-14, 2016.

T. Dallenga and U. E. Schaible, Neutrophils in tuberculosis-first line of defence or booster of disease and targets for host-directed therapy?, vol.74, p.12, 2016.

R. D. Pechous, With friends like these: the complex role of neutrophils in the progression of severe pneumonia. Front Cell Infect Microbiol, vol.7, p.160, 2017.

F. Cavalla, C. Biguetti, S. Jain, C. Johnson, A. Letra et al., Proteomic profiling and differential messenger RNA expression correlate HSP27 and serpin family B member 1 to apical periodontitis outcomes, J Endodont, vol.43, pp.1486-93, 2017.

M. K. Singh, B. Sharma, and P. K. Tiwari, The small heat shock protein Hsp27: present understanding and future prospects, J Therm Biol, vol.69, pp.149-54, 2017.

M. Baumann, C. T. Pham, and C. Benarafa, SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G, Blood, vol.121, pp.3900-3907, 2013.

G. P. Garlet, R. Horwat, H. L. Ray, T. P. Garlet, E. M. Silveira et al., Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature, J Endodont, vol.38, pp.185-90, 2012.

S. A. Al-dujaili, E. Lau, H. Al-dujaili, K. Tsang, A. Guenther et al., Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro, J Cell Biochem, vol.112, pp.2412-2435, 2011.

C. Hayashida, J. Ito, M. Nakayachi, M. Okayasu, Y. Ohyama et al., Osteocytes produce interferon-beta as a negative regulator of osteoclastogenesis, J Biol Chem, vol.289, pp.11545-55, 2014.

S. Zhao, Y. K. Zhang, S. Harris, S. S. Ahuja, and L. F. Bonewald, MLO-Y4 osteocyte-like cells support osteoclast formation and activation, J Bone Mineral Res, vol.17, pp.2068-79, 2002.

P. R. Buenzli and N. A. Sims, Quantifying the osteocyte network in the human skeleton, Bone, vol.75, pp.144-50, 2015.

N. Ito, A. R. Wijenayaka, M. Prideaux, M. Kogawa, R. T. Ormsby et al., Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli, Mol Cell Endocrinol, vol.399, pp.208-226, 2015.

K. Algate, D. R. Haynes, P. M. Bartold, T. N. Crotti, and M. D. Cantley, The effects of tumour necrosis factor-alpha on bone cells involved in periodontal alveolar bone loss; osteoclasts, osteoblasts and osteocytes, J Periodontal Res, vol.51, pp.549-66, 2016.

M. Baeza, M. Garrido, P. Hernandez-rios, A. Dezerega, J. Garcia-sesnich et al., Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: an exploratory study, J Clin Periodontol, vol.43, pp.34-45, 2016.

S. Corbella, P. Veronesi, V. Galimberti, R. Weinstein, D. Fabbro et al., Is periodontitis a risk indicator for cancer? A meta-analysis, PLoS ONE, vol.13, p.195683, 2018.

M. S. Tonetti and T. E. Van-dyke, Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases, J Periodontol, vol.84, pp.24-33, 2013.

, Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions, Br Dental J, vol.225, p.141, 2018.

M. Sanz, A. Ceriello, M. Buysschaert, I. Chapple, R. T. Demmer et al., Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology, J Clin Periodontol, vol.45, pp.138-187, 2018.

M. S. Gomes, T. C. Blattner, &. Sant, M. Filho, F. S. Grecca et al., Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis, J Endodont, vol.39, pp.1205-1222, 2013.

M. Garrido, A. M. Cardenas, J. Astorga, F. Quinlan, M. Valdes et al., Elevated systemic inflammatory burden and cardiovascular risk in young adults with endodontic apical lesions, J Endodont, vol.45, pp.111-116, 2019.

H. A. Schenkein and B. G. Loos, Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases, J Clin Periodontol, pp.51-69, 2013.

M. Garrido, A. Dezerega, M. J. Bordagaray, M. Reyes, R. Vernal et al., C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6, J Endodont, vol.41, pp.464-473, 2015.

P. Hernandez-rios, P. J. Pussinen, R. Vernal, and M. Hernandez, Oxidative stress in the local and systemic events of apical periodontitis, Front Physiol, vol.8, p.869, 2017.

N. Buduneli and D. F. Kinane, Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis, J Clin Periodontol, issue.11, pp.85-105, 2011.

T. Sorsa, U. K. Gursoy, S. Nwhator, M. Hernandez, T. Tervahartiala et al., Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases, Periodontology, vol.70, pp.142-63, 2000.

N. Rathnayake, D. R. Gieselmann, A. M. Heikkinen, T. Tervahartiala, and T. Sorsa, Salivary Diagnostics-point-of-care diagnostics of MMP-8 in dentistry and medicine, Diagnostics, vol.7, p.7, 2017.

J. M. Leppilahti, U. Harjunmaa, J. Jarnstedt, C. Mangani, M. Hernandez et al., Diagnosis of newly delivered mothers for periodontitis with a novel oral-rinse aMMP-8 point-of-care test in a rural malawian population, Diagnostics, vol.8, p.67, 2018.

S. Alassiri, P. Parnanen, N. Rathnayake, G. Johannsen, A. M. Heikkinen et al., The ability of quantitative, specific, and sensitive point-of-care/chairside oral fluid immunotests for aMMP-8 to detect periodontal and periimplant diseases, Dis Mark, p.1306396, 2018.

T. Sorsa, D. Gieselmann, N. B. Arweiler, and M. Hernandez, A quantitative pointof-care test for periodontal and dental peri-implant diseases. Nat Rev Dis Primers, vol.3, p.17069, 2017.

A. Chaparro, A. Sanz, A. Quintero, C. Inostroza, V. Ramirez et al., Increased inflammatory biomarkers in early pregnancy is associated with the development of pre-eclampsia in patients with periodontitis: a case control study, J Periodontal Res, vol.48, pp.302-309, 2013.

A. Chaparro, E. Zuniga, M. Varas-godoy, D. Albers, V. Ramirez et al., Periodontitis and placental growth factor in oral fluids are early pregnancy predictors of gestational diabetes mellitus, J Periodontol, vol.89, pp.1052-60, 2018.

J. B. Payne, L. M. Golub, J. A. Stoner, H. M. Lee, R. A. Reinhardt et al., The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial, J Am Dental Assoc, vol.142, pp.262-73, 2011.

E. Cotti, C. Dessi, A. Piras, G. Flore, M. Deidda et al., Association of endodontic infection with detection of an initial lesion to the cardiovascular system, J Endodont, vol.37, pp.1624-1633, 2011.

P. Heikkila, A. But, T. Sorsa, and J. Haukka, Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults in 10-year follow-up, Int J Cancer, vol.142, pp.2244-53, 2018.

S. G. Damle, Health consequences of poor oral health?, Contemp Clin Dent, vol.9, p.1, 2018.

M. Hormia, J. Willberg, H. Ruokonen, and S. Syrjanen, Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa, J Periodontol, vol.76, pp.358-63, 2005.

I. Saygun, A. Kubar, A. Ozdemir, and J. Slots, Periodontitis lesions are a source of salivary cytomegalovirus and Epstein-Barr virus, J Periodontal Res, vol.40, pp.187-91, 2005.

J. Katz, M. D. Onate, K. M. Pauley, I. Bhattacharyya, and S. Cha, Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma, Int J Oral Sci, vol.3, pp.209-224, 2011.

M. T. Nieminen, D. Listyarifah, J. Hagstrom, C. Haglund, D. Grenier et al., Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation, Br J Cancer, vol.118, pp.428-462, 2018.

A. K. Kylma, L. Jouhi, D. Listyarifah, H. Mohamed, A. Makitie et al., Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma, Br J Cancer, vol.119, pp.89-95, 2018.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon et al., Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the, American Heart Association. Circulation, vol.107, pp.499-511, 2003.

D. L. Brown, K. K. Desai, B. A. Vakili, C. Nouneh, H. M. Lee et al., Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial, Arterioscler Thromb Vasc Biol, vol.24, pp.733-741, 2004.

T. J. Bench, J. A. Brown, D. L. Golub, L. M. Evans, R. T. Mcnamara et al., A non-antimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis, Pharmacol Res, vol.64, pp.561-567, 2011.

A. Ann, . Sci, L. M. Golub, H. M. Lee, J. A. Stoner et al., Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women, J Periodontol, vol.732, pp.1409-1427, 1994.

J. A. Hamilton, H. Hasturk, A. Kantarci, and C. N. Serhan, Van Dyke T. Atherosclerosis, periodontal disease, and treatment with resolvins, Curr Atheroscl Rep, vol.19, p.57, 2017.

E. The, Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up ?, Ann Oncol, vol.23, issue.suppl_7, pp.100-109, 2012.

A. A. Razek, Imaging appearance of bone tumors of the maxillofacial region, World J Radiol, vol.3, pp.125-159, 2011.

J. M. Wright and M. Vered, Update from the 4th edition of the World Health Organization classification of head and neck tumours: odontogenic and maxillofacial bone tumors, Head Neck Pathol, vol.11, pp.68-77, 2017.

H. Bertin, R. Guilho, R. Brion, J. Amiaud, S. Battaglia et al., Jaw osteosarcoma models in mice: first description, J Transl Med, vol.17, p.56, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-02053605

Y. K. Park, K. N. Ryu, H. R. Park, and D. W. Kim, Low-grade osteosarcoma of the maxillary sinus, Skeletal Radiol, vol.32, pp.161-165, 2003.

E. David, F. Blanchard, M. F. Heymann, D. Pinieux, G. Gouin et al., The bone niche of chondrosarcoma: a sanctuary for drug resistance, tumour growth and also a source of new therapeutic targets, Sarcoma, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00667904

H. K. Brown, K. Schiavone, F. Gouin, M. F. Heymann, and D. Heymann, Biology of bone sarcomas and new therapeutic developments, Calci Tiss Int, vol.102, pp.174-95, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01653600

C. Chan, G. S. Gulati, R. Sinha, J. V. Tompkins, M. Lopez et al., Identification of the human skeletal stem cell, Cell, vol.175, pp.43-56, 2018.

S. Gambera, A. Abarrategi, F. Gonzalez-camacho, A. Morales-molina, R. J. Alfranca et al., Clonal dynamics in osteosarcoma defined by RGB marking, Nat Commun, vol.9, p.3994, 2018.

H. K. Brown, M. Tellez-gabriel, and D. Heymann, Cancer stem cells in osteosarcoma, Cancer Lett, vol.386, pp.189-95, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-01466078

F. M. Vallette, C. Olivier, F. Lezot, L. Oliver, D. Cochonneau et al., Dormant, quiescent, tolerant and persister cells: four synonyms for the same target in cancer, Biochem Pharmacol, vol.162, pp.169-76, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01947474

C. Dumars, J. M. Ngyuen, A. Gaultier, R. Lanel, N. Corradini et al., Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma, Oncotarget, vol.7, pp.78343-54, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01466103

M. F. Heymann, F. Lezot, and D. Heymann, The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma, Cell Immunol, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-01644725

P. Koirala, M. E. Roth, J. Gill, S. Piperdi, J. M. Chinai et al., Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma, Sci Rep, vol.6, p.30093, 2016.

B. Fritzsching, J. Fellenberg, L. Moskovszky, Z. Sapi, T. Krenacs et al., CD8(+)/FOXP3(+)-ratio in osteosarcoma microenvironment separates survivors from non-survivors: a multicenter validated retrospective study, Oncoimmunology, vol.4, p.990800, 2015.

A. Stamatopoulos, T. Stamatopoulos, Z. Gamie, E. Kenanidis, R. Ribeiro et al., Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice, J Bone Oncol, vol.16, p.100231, 2019.

S. R. Baglio, T. Lagerweij, M. Perez-lanzon, X. D. Ho, N. Leveille et al., Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression, Clin Cancer Res, vol.23, pp.3721-3754, 2017.

S. Avnet, D. Pompo, G. Chano, T. Errani, C. Ibrahim-hashim et al., Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-kappaB activation, Int J Cancer, vol.140, pp.1331-1376, 2017.

N. Renema, B. Navet, M. F. Heymann, F. Lezot, and D. Heymann, RANK-RANKL signalling in cancer, Biosci Rep, vol.36, p.366, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01644732

B. Navet, K. Ando, J. W. Vargas-franco, R. Brion, J. Amiaud et al., The intrinsic and extrinsic implications of RANKL/RANK signaling in osteosarcoma: from tumor initiation to lung metastases, Cancers, vol.10, p.398, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-02102610

Y. Chen, D. Grappa, M. A. Molyneux, S. D. Mckee, T. D. Waterhouse et al., RANKL blockade prevents and treats aggressive osteosarcomas, Sci Transl Med, vol.7, pp.317-197, 2015.

M. F. Heymann, H. K. Brown, and D. Heymann, Drugs in early clinical development for the treatment of osteosarcoma, Expert Opin Investigat Drugs, vol.25, pp.1265-80, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01466096

D. Heymann, Metastatic osteosarcoma challenged by regorafenib, Lancet Oncol, vol.20, pp.12-16, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01947468

R. F. Loeser, S. R. Goldring, C. R. Scanzello, and M. B. Goldring, Osteoarthritis: a disease of the joint as an organ, Arthritis Rheum, vol.64, pp.1697-707, 2012.

L. M. Vos, R. Kuijer, H. Slater, J. J. Bulstra, S. K. Stegenga et al., Inflammation is more distinct in temporomandibular joint osteoarthritis compared to the knee joint, J Oral Maxillofac Surg, vol.72, pp.35-40, 2014.

K. D. Allen and Y. M. Golightly, State of the evidence, Curr Opin Rheumatol, vol.27, pp.276-83, 2015.
URL : https://hal.archives-ouvertes.fr/in2p3-00166974

V. L. Johnson and D. J. Hunter, The epidemiology of osteoarthritis, Best Pract Res Clin Rheumatol, vol.28, pp.5-15, 2014.

E. Tanaka, M. S. Detamore, and L. G. Mercuri, Degenerative disorders of the temporomandibular joint: etiology, diagnosis, and treatment, J Dental Res, vol.87, pp.296-307, 2008.

M. C. Embree, T. M. Kilts, M. Ono, C. A. Inkson, F. Syed-picard et al., Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis, Am J Pathol, vol.176, pp.812-838, 2010.

G. Yee, Y. Yu, W. R. Walsh, R. Lindeman, and M. D. Poole, The immunolocalisation of VEGF in the articular cartilage of sheep mandibular condyles, J Craniomaxillofac Surg, vol.31, pp.244-51, 2003.

R. Matsumoto, H. Ioi, T. K. Goto, A. Hara, S. Nakata et al., Relationship between the unilateral TMJ osteoarthritis/osteoarthrosis, mandibular asymmetry and the EMG activity of the masticatory muscles: a retrospective study, J Oral Rehabil, vol.37, pp.85-92, 2010.

Z. Krisjane, I. Urtane, G. Krumina, L. Neimane, and I. Ragovska, The prevalence of TMJ osteoarthritis in asymptomatic patients with dentofacial deformities: a cone-beam CT study, Int J Oral Maxillofacial Surg, vol.41, pp.690-695, 2012.

B. F. Betti, V. Everts, J. Ket, H. Tabeian, A. D. Bakker et al., Effect of mechanical loading on the metabolic activity of cells in the temporomandibular joint: a systematic review, Clin Oral Investig, vol.22, pp.57-67, 2018.

A. Utreja, N. A. Dyment, S. Yadav, M. M. Villa, Y. Li et al., Cell and matrix response of temporomandibular cartilage to mechanical loading, Osteoarthr Cartilage, vol.24, pp.335-379, 2016.

T. Fujisawa, T. Kuboki, T. Kasai, W. Sonoyama, S. Kojima et al., A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint, J Dental Res, vol.82, pp.731-736, 2003.

T. Sobue, W. C. Yeh, A. Chhibber, A. Utreja, V. Diaz-doran et al., Murine TMJ loading causes increased proliferation and chondrocyte maturation, J Dental Res, vol.90, pp.512-518, 2011.

G. D. Nicodemus, I. Villanueva, and S. J. Bryant, Mechanical stimulation of TMJ condylar chondrocytes encapsulated in PEG hydrogels, J Biomed Mater Res A, vol.83, pp.323-354, 2007.

H. Ichimiya, T. Takahashi, W. Ariyoshi, H. Takano, T. Matayoshi et al., Compressive mechanical stress promotes osteoclast formation through RANKL expression on synovial cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, vol.103, pp.334-375, 2007.

T. Shinohara, T. Izawa, A. Mino-oka, H. Mori, A. Iwasa et al., Hyaluronan metabolism in overloaded temporomandibular joint, J Oral Rehabil, vol.43, pp.921-929, 2016.

A. C. Petrey and C. A. De-la-motte, Hyaluronan, a crucial regulator of inflammation, Front Immunol, vol.5, p.101, 2014.

K. A. Scheibner, M. A. Lutz, S. Boodoo, M. J. Fenton, J. D. Powell et al., Hyaluronan fragments act as an endogenous danger signal by engaging TLR2, J Immunol, vol.177, pp.1272-81, 2006.

X. D. Wang, J. N. Zhang, Y. H. Gan, and Y. H. Zhou, Current understanding of pathogenesis and treatment of TMJ osteoarthritis, J Dental Res, vol.94, pp.666-73, 2015.

R. F. De-souza, L. Da-silva, C. H. Nasser, M. Fedorowicz, Z. et al., Interventions for the management of temporomandibular joint osteoarthritis, Cochrane Database Syst Rev, p.7261, 2012.

L. I. Sakkas and C. D. Platsoucas, The role of T cells in the pathogenesis of osteoarthritis, Arthritis Rheum, vol.56, pp.409-433, 2007.

B. J. De-lange-brokaar, A. Ioan-facsinay, G. J. Van-osch, A. M. Zuurmond, J. Schoones et al., Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review, Osteoarthr Cartilage, vol.20, pp.1484-99, 2012.

F. Ponchel, A. N. Burska, E. M. Hensor, R. Raja, M. Campbell et al., Changes in peripheral blood immune cell composition in osteoarthritis, Osteoarthr Cartilage, vol.23, pp.1870-1878, 2015.

F. Pessler, L. X. Chen, L. Dai, C. Gomez-vaquero, C. Diaz-torne et al., A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans' Illness and joint pain compared to normal and osteoarthritis synovium, Clin Rheumatol, vol.27, pp.1127-1161, 2008.

K. Kaneyama, N. Segami, M. Nishimura, T. Suzuki, and J. Sato, Importance of proinflammatory cytokines in synovial fluid from 121 joints with temporomandibular disorders, Br J Oral Maxillofac Surg, vol.40, pp.418-441, 2002.

S. V. Kellesarian, V. R. Malignaggi, T. Abduljabbar, F. Vohra, H. Malmstrom et al., Efficacy of scaling and root planing with and without adjunct antimicrobial photodynamic therapy on the expression of cytokines in the gingival crevicular fluid of patients with periodontitis: a systematic review, Photodiagnosis Photodyn Ther, vol.16, pp.76-84, 2016.

W. H. Lim, J. Toothman, J. H. Miller, R. H. Tallents, S. M. Brouxhon et al., IL-1beta inhibits TGFbeta in the temporomandibular joint, J Dental Res, vol.88, pp.557-62, 2009.

R. Vernal, E. Velasquez, J. Gamonal, J. A. Garcia-sanz, A. Silva et al., Expression of proinflammatory cytokines in osteoarthritis of the temporomandibular joint, Arch Oral Biol, vol.53, pp.910-915, 2008.

S. Kaya, G. , Y. Yavuz, G. Kiziltunc, and A. , Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders, J Oral Rehabil, vol.45, pp.289-94, 2018.

M. Kalladka, S. Quek, G. Heir, E. Eliav, M. Mupparapu et al., Temporomandibular joint osteoarthritis: diagnosis and long-term conservative management: a topic review, J Indian Prosthodont Soc, vol.14, pp.6-15, 2014.

W. H. Robinson, C. M. Lepus, Q. Wang, H. Raghu, R. Mao et al., Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis, Nat Rev Rheumatol, vol.12, pp.580-92, 2016.

G. Y. Chen and G. Nunez, Sterile inflammation: sensing and reacting to damage, Nat Rev Immunol, vol.10, pp.826-863, 2010.

S. B. Milam, Pathogenesis of degenerative temporomandibular joint arthritides, Odontology, vol.93, pp.7-15, 2005.

S. B. Milam, G. Zardeneta, and J. P. Schmitz, Oxidative stress and degenerative temporomandibular joint disease: a proposed hypothesis, J Oral Maxillofac Surg, vol.56, pp.214-237, 1998.

L. Wei, H. Xiong, B. Li, Z. Gong, J. Li et al., Change of HA molecular size and boundary lubrication in synovial fluid of patients with temporomandibular disorders, J Oral Rehabil, vol.37, pp.271-278, 2010.

T. Takahashi, K. Tominaga, H. Takano, W. Ariyoshi, M. Habu et al., A decrease in the molecular weight of hyaluronic acid in synovial fluid from patients with temporomandibular disorders, J Oral Pathol Med, vol.33, pp.224-233, 2004.

D. Jiang, J. Liang, J. Fan, S. Yu, S. Chen et al., Regulation of lung injury and repair by Toll-like receptors and hyaluronan, Nature Med, vol.11, pp.1173-1182, 2005.

C. R. Scanzello and S. R. Goldring, The role of synovitis in osteoarthritis pathogenesis, Bone, vol.51, pp.249-57, 2012.

J. Kong, Y. Yang, S. Sun, J. Xie, X. Lin et al., Effect of toll-like receptor 4 on synovial injury of temporomandibular joint in rats caused by occlusal interference, p.7694921, 2016.

X. Lin, J. Xie, S. Sun, X. Ren, J. Kong et al., Toll-Like Receptor 4 (TLR4) stimulates synovial injury of temporomandibular joint in rats through the activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway, Med Sci Monit, vol.24, pp.4405-4417, 2018.

H. A. Israel, B. Diamond, F. Saed-nejad, and A. Ratcliffe, Osteoarthritis and synovitis as major pathoses of the temporomandibular joint: comparison of clinical diagnosis with arthroscopic morphology, J Oral Maxillofac Surg, vol.56, pp.1023-1030, 1998.

H. A. Israel, C. J. Langevin, M. D. Singer, and D. A. Behrman, The relationship between temporomandibular joint synovitis and adhesions: pathogenic mechanisms and clinical implications for surgical management, J Oral Maxillofac Surg, vol.64, pp.1066-74, 2006.

T. Hattori, N. Ogura, M. Akutsu, M. Kawashima, S. Watanabe et al., Gene expression profiling of IL-17A-treated synovial fibroblasts from the human temporomandibular joint, p.436067, 2015.

S. K. Chang, Z. Gu, and M. B. Brenner, Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11, Immunol Rev, vol.233, pp.256-66, 2010.

C. D. Buckley, D. W. Gilroy, and C. N. Serhan, Proresolving lipid mediators and mechanisms in the resolution of acute inflammation, Immunity, vol.40, pp.315-342, 2014.

R. Axmann, C. Bohm, G. Kronke, J. Zwerina, J. Smolen et al., Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo, Arthritis Rheum, vol.60, pp.2747-56, 2009.

A. Kimura and T. Kishimoto, IL-6: regulator of Treg/Th17 balance, Eur J Immunol, vol.40, pp.1830-1835, 2010.

H. Takayanagi, H. Iizuka, T. Juji, T. Nakagawa, A. Yamamoto et al., Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis, Arthritis Rheum, vol.43, pp.259-69, 2000.

K. Kaneyama, N. Segami, J. Sato, H. Yoshimura, and R. Nishiura, Expression of receptor activator of nuclear factor-kappaB ligand in synovial tissue: comparison with degradation of articular cartilage in temporomandibular joint disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, vol.104, pp.12-19, 2007.

L. Danks, N. Komatsu, M. M. Guerrini, S. Sawa, M. Armaka et al., RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation, Ann Rheumat Dis, vol.75, pp.1187-95, 2016.

K. Jiao, L. N. Niu, M. Q. Wang, J. Dai, S. B. Yu et al., Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats, Bone, vol.48, pp.362-71, 2011.

K. R. Taylor, K. Yamasaki, K. A. Radek, D. Nardo, A. Goodarzi et al., Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2, J Biol Chem, vol.282, pp.18265-75, 2007.

C. Termeer, F. Benedix, J. Sleeman, C. Fieber, U. Voith et al., Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor

, J Exp Med, vol.195, pp.99-111, 2002.

C. C. Termeer, J. Hennies, U. Voith, T. Ahrens, J. M. Weiss et al., Oligosaccharides of hyaluronan are potent activators of dendritic cells, J Immunol, vol.165, pp.1863-70, 2000.

R. Galandrini, E. Galluzzo, N. Albi, C. E. Grossi, and A. Velardi, Hyaluronate is costimulatory for human T cell effector functions and binds to CD44 on activated T cells, J Immunol, vol.153, pp.21-31, 1994.

M. Rizzo, J. Bayo, F. Piccioni, M. Malvicini, E. Fiore et al., Low molecular weight hyaluronan-pulsed human dendritic cells showed increased migration capacity and induced resistance to tumor chemoattraction, PLoS ONE, vol.9, p.107944, 2014.

G. Monasterio, J. Guevara, J. P. Ibarra, F. Castillo, J. Diaz-zuniga et al., Immunostimulatory activity of low-molecularweight hyaluronan on dendritic cells stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis, Front Immunol, vol.23, p.533, 2015.

E. K. Persson, H. Uronen-hansson, M. Semmrich, A. Rivollier, K. Hagerbrand et al., IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation, Immunity, vol.38, pp.958-69, 2013.

J. A. Symons, J. F. Mcculloch, N. C. Wood, and G. W. Duff, Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis, Clin Immunol Immunopathol, vol.60, pp.72-82, 1991.

H. De-jong, S. E. Berlo, P. Hombrink, H. G. Otten, W. Van-eden et al., Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis, Ann Rheumat Dis, vol.69, pp.255-62, 2010.

G. Monasterio, F. Castillo, L. Rojas, E. A. Cafferata, C. Alvarez et al., Th1/Th17/Th22 immune response and their association with joint pain, imagenological bone loss, RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: a preliminary report, J Oral Rehabil, vol.45, pp.589-97, 2018.

C. A. Murphy, C. L. Langrish, Y. Chen, W. Blumenschein, T. Mcclanahan et al., Divergent pro-and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation, J Exp Med, vol.198, pp.1951-1958, 2003.

S. Nakae, A. Nambu, K. Sudo, and Y. Iwakura, Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice, J Immunol, vol.171, pp.6173-6180, 2003.

S. Nakae, S. Saijo, R. Horai, K. Sudo, S. Mori et al., IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist, Proc Natl Acad Sci, vol.100, pp.5986-90, 2003.

A. Lurati, A. Laria, A. Gatti, B. Brando, and M. Scarpellini, Different T cells' distribution and activation degree of Th17 CD4+ cells in peripheral blood in patients with osteoarthritis, rheumatoid arthritis, and healthy donors: preliminary results of the MAGENTA CLICAO study, Open Access Rheumatol, vol.7, pp.63-71, 2015.

H. Yamada, Y. Nakashima, K. Okazaki, T. Mawatari, J. Fukushi et al., Preferential accumulation of activated Th1 cells not only in rheumatoid arthritis but also in osteoarthritis joints, J Rheumatol, vol.38, pp.1569-75, 2011.

K. Nistala, S. Adams, H. Cambrook, S. Ursu, B. Olivito et al., Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment, Proc Natl Acad Sci USA, vol.107, pp.14751-14757, 2010.

A. Penatti, F. Facciotti, D. Matteis, R. Larghi, P. Paroni et al., Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis, Arthritis Res Ther, vol.19, p.103, 2017.

M. R. Hussein, N. A. Fathi, A. M. El-din, H. I. Hassan, F. Abdullah et al., Alterations of the CD4(+), CD8 (+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factor-alpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations, Pathol Oncol Res, vol.14, pp.321-329, 2008.

S. Sarkar, J. S. Brucks, M. Endres, J. Fox, D. A. Zhou et al., Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis, Clin Exp Immunol, vol.177, pp.652-61, 2014.

K. Kaneyama, N. Segami, J. Sato, M. Nishimura, and H. Yoshimura, Interleukin-6 family of cytokines as biochemical markers of osseous changes in the temporomandibular joint disorders, Br J Oral Maxillofac Surg, vol.42, pp.246-50, 2004.

E. M. Moran, R. Mullan, J. Mccormick, M. Connolly, O. Sullivan et al., Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies, Arthritis Res Ther, vol.11, p.113, 2009.

M. L. Toh, G. Gonzales, M. I. Koenders, A. Tournadre, D. Boyle et al., Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression, PLoS ONE, vol.5, p.13416, 2010.

G. Q. Li, Y. Zhang, D. Liu, Y. Y. Qian, H. Zhang et al., Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like synoviocyte migration and invasion through suppression of NF-kappaB-mediated matrix metalloproteinase-9 expression, Int Immunopharmacol, vol.14, pp.422-453, 2012.

Y. Chen, M. Zhong, L. Liang, F. Gu, and H. Peng, Interleukin-17 induces angiogenesis in human choroidal endothelial cells in vitro, Invest Ophthalmol Vis Sci, vol.55, pp.6968-75, 2014.

K. Sato, A. Suematsu, K. Okamoto, A. Yamaguchi, Y. Morishita et al., Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction, J Exp Med, vol.203, pp.2673-82, 2006.

M. B. Schaffler, W. Y. Cheung, R. Majeska, and O. Kennedy, Osteocytes: master orchestrators of bone, Calcif Tissue Int, vol.94, pp.5-24, 2014.

J. Xiong, M. Piemontese, M. Onal, J. Campbell, J. J. Goellner et al., not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone, PLoS ONE, vol.10, p.138189, 2015.

I. Kramer, C. Halleux, H. Keller, M. Pegurri, J. H. Gooi et al., Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis, Mol Cell Biol, vol.30, pp.3071-85, 2010.

A. Shoji-matsunaga, T. Ono, M. Hayashi, H. Takayanagi, K. Moriyama et al., Osteocyte regulation of orthodontic force-mediated tooth movement via RANKL expression. Sci Rep, vol.7, p.8753, 2017.

M. Inoue, T. Ono, Y. Kameo, F. Sasaki, T. Ono et al., Forceful mastication activates osteocytes and builds a stout jawbone, Sci Rep, vol.9, p.4404, 2019.

I. Prasadam, S. Farnaghi, J. Q. Feng, W. Gu, S. Perry et al., Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrinbeta1 and focal adhesion kinase signaling cues, Arthritis Res Ther, vol.15, p.150, 2013.

T. Wakita, M. Mogi, K. Kurita, M. Kuzushima, and A. Togari, Increase in RANKL: OPG ratio in synovia of patients with temporomandibular joint disorder, J Dental Res, vol.85, pp.627-659, 2006.

H. Takayanagi, Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems, Nat Rev Immunol, vol.7, pp.292-304, 2007.

H. Takayanagi, Osteoimmunology and the effects of the immune system on bone, Nat Rev Rheumatol, vol.5, pp.667-76, 2009.

J. Kikuta, Y. Wada, T. Kowada, Z. Wang, G. H. Sun-wada et al., Dynamic visualization of RANKL and Th17-mediated osteoclast function, J Clin Invest, vol.123, pp.866-73, 2013.

E. Schiffman, R. Ohrbach, E. Truelove, J. Look, G. Anderson et al., Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: recommendations of the international RDC/TMD Consortium Network * and orofacial pain special interest groupdagger, J Oral & Facial Pain Headache, vol.28, pp.6-27, 2014.

Y. K. Kim, S. G. Kim, B. S. Kim, J. Y. Lee, P. Y. Yun et al., Analysis of the cytokine profiles of the synovial fluid in a normal temporomandibular joint: preliminary study, J Craniomaxillofac Surg, vol.40, pp.337-378, 2012.

T. Takahashi, T. Kondoh, M. Fukuda, Y. Yamazaki, T. Toyosaki et al., Proinflammatory cytokines detectable in synovial fluids from patients with temporomandibular disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, vol.85, pp.135-176, 1998.

S. Kotake, N. Udagawa, N. Takahashi, K. Matsuzaki, K. Itoh et al., IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis, The Journal of clinical investigation, vol.103, pp.1345-52, 1999.

K. Tanimoto, A. Suzuki, S. Ohno, K. Honda, N. Tanaka et al., Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint, J Dental Res, vol.83, pp.40-44, 2004.

S. Kuroda, K. Tanimoto, T. Izawa, S. Fujihara, J. H. Koolstra et al., Biomechanical and biochemical characteristics of the mandibular condylar cartilage, Osteoarthr Cartilage, vol.17, pp.1408-1423, 2009.

T. Nakano and P. G. Scott, Changes in the chemical composition of the bovine temporomandibular joint disc with age, Arch Oral Biol, vol.41, pp.845-53, 1996.

M. Jibiki, S. Shimoda, Y. Nakagawa, K. Kawasaki, K. Asada et al., Calcifications of the disc of the temporomandibular joint, J Oral Pathol Med, vol.28, pp.413-422, 1999.

Y. Takano, Y. Moriwake, Y. Tohno, T. Minami, S. Tohno et al., Age-related changes of elements in the human articular disk of the temporomandibular joint, Biol Trace Element Res, vol.67, pp.269-76, 1999.

T. Pufe, V. Harde, W. Petersen, M. B. Goldring, B. Tillmann et al., Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes, J Pathol, vol.202, pp.367-74, 2004.