H. Schumacher, A. Somlyo, R. Tse, and K. Maurer, Arthritis Associated with Apatite Crystals, Annals of Internal Medicine, vol.87, issue.4, pp.411-416, 1977.
DOI : 10.7326/0003-4819-87-4-411

D. Mccarty and R. Gatter, Recurrent acute inflammation associated with focal apatite crystal deposition, Arthritis & Rheumatism, vol.48, issue.6, pp.804-819, 1966.
DOI : 10.1002/art.1780090608

H. Schumacher, J. Miller, C. Ludivico, and R. Jessar, Erosive arthritis associated with apatite crystal deposition, Arthritis & Rheumatism, vol.203, issue.1, pp.31-37, 1981.
DOI : 10.1002/art.1780240105

D. Mccarty, P. Halverson, G. Carrera, B. Brewer, and F. Kozin, ???Milwaukee shoulder??????association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. i. clinical aspects, Arthritis & Rheumatism, vol.31, issue.3, pp.464-473, 1981.
DOI : 10.1002/art.1780240303

P. Halverson, H. Cheung, D. Mccarty, J. Garancis, and N. Mandel, ???Milwaukee shoulder??????association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. ii. synovial fluid studies, Arthritis & Rheumatism, vol.133, issue.3, pp.474-483, 1981.
DOI : 10.1002/art.1780240304

J. Garancis, H. Cheung, P. Halverson, and D. Mccarty, ???Milwaukee shoulder??????association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. iii. morphologic and biochemical studies of an excised synovium showing chondromatosis, Arthritis & Rheumatism, vol.56, issue.3, pp.484-491, 1981.
DOI : 10.1002/art.1780240305

B. Derfus, J. Kurian, J. Butler, L. Daft, G. Carrera et al., The high prevalence of pathologic calcium crystals in pre-operatives knees, J Rheumatol, vol.29, pp.570-574, 2002.

P. Halverson and D. Mccarty, Patterns of radiographic abnormalities associated with basic calcium phosphate and calcium pyrophosphate dihydrate crystal deposition in the knee., Annals of the Rheumatic Diseases, vol.45, issue.7, pp.603-605, 1986.
DOI : 10.1136/ard.45.7.603

F. Rutsch and R. Terkeltaub, Deficiencies of physiologic calcification inhibitors and low-grade inflammation in arterial calcification: lessons for cartilage calcification, Joint Bone Spine, vol.72, issue.2, pp.110-118, 2005.
DOI : 10.1016/j.jbspin.2004.05.014

H. Cheung, V. Wyk, J. Russell, W. Mccarty, and D. , Mitogenic activity of hydroxyapatite: Requirement for somatomedin C, Journal of Cellular Physiology, vol.112, issue.2, pp.143-148, 1986.
DOI : 10.1002/jcp.1041280202

P. Mitchell, W. Pledger, and H. Cheung, Molecular mechanism of basic calcium phosphate crystal-induced mitogenesis. Role of protein kinase C, J Biol Chem, vol.264, pp.14071-14077, 1989.

P. Mitchell, J. Struve, G. Mccarthy, and H. Cheung, Basic calcium phosphate crystals stimulate cell proliferation and collagenase message accumulation in cultured adult articular chondrocytes, Arthritis & Rheumatism, vol.10, issue.3, pp.343-350, 1992.
DOI : 10.1002/art.1780350314

H. Cheung, P. Halverson, and D. Mccarty, Phagocytosis of Hydroxyapatite or Calcium Pyrophosphate Dihydrate Crystals by Rabbit Articular Chondrocytes Stimulates Release of Collagenase, Neutral Protease, and Prostaglandins E2 and F2??, Experimental Biology and Medicine, vol.173, issue.2, pp.181-189, 1983.
DOI : 10.3181/00379727-173-41628

G. Mccarthy, P. Mitchell, and H. Cheung, The mitogenic response to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase in human fibroblasts, Arthritis & Rheumatism, vol.27, issue.8, pp.1021-1030, 1991.
DOI : 10.1002/art.1780340812

G. Mccarthy, P. Mitchell, J. Struve, and H. Cheung, Basic calcium phosphate crystals cause coordinate induction and secretion of collagenase and stromelysin, Journal of Cellular Physiology, vol.84, issue.1, pp.140-146, 1992.
DOI : 10.1002/jcp.1041530118

G. Mccarthy, P. Westfall, I. Masuda, P. Christopherson, H. Cheung et al., Basic calcium phosphate crystals activate human osteoarthritic synovial fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult porcine articular chondrocytes, Annals of the Rheumatic Diseases, vol.60, issue.4, pp.399-406, 2001.
DOI : 10.1136/ard.60.4.399

G. Bai, D. Howell, B. Roos, G. Howard, and H. Cheung, Basic calcium phosphate crystals up-regulate metalloproteinases but down-regulate tissue inhibitor of metalloproteinase-1 and -2 in human fibroblasts, Osteoarthritis and Cartilage, vol.9, issue.5, pp.416-422, 2001.
DOI : 10.1053/joca.2000.0407

P. Reuben, L. Wenger, M. Cruz, and H. Cheung, Induction of Matrix Metalloproteinase-8 in Human Fibroblasts by Basic Calcium Phosphate and Calcium Pyrophosphate Dihydrate Crystals: Effect of Phosphocitrate, Connective Tissue Research, vol.261, issue.1, pp.1-12, 2001.
DOI : 10.1002/(SICI)1097-4652(199908)180:2<215::AID-JCP9>3.0.CO;2-J

P. Reuben, M. Brogley, Y. Sun, and H. Cheung, Molecular mechanism of the induction of metalloproteinases 1 and 3 in human fibroblasts by basic calcium phosphate crystals. Role of calcium-dependent protein kinase C?, J Biol Chem, vol.277, pp.15190-15198, 2002.

Y. Sun, L. Wenger, C. Brinckerhoff, R. Misra, and H. Cheung, Basic Calcium Phosphate Crystals Induce Matrix Metalloproteinase-1 through the Ras/Mitogen-activated Protein Kinase/c-Fos/AP-1/Metalloproteinase 1 Pathway: INVOLVEMENT OF TRANSCRIPTION FACTOR BINDING SITES AP-1 AND PEA-3, Journal of Biological Chemistry, vol.277, issue.2, pp.1544-1552, 2002.
DOI : 10.1074/jbc.M100567200

J. Dayer, V. Evequoz, C. Zavadil-grob, M. Grynpas, P. Cheng et al., Effect of synthetic calcium pyrophosphate and hydroxyapatite crystals on the interaction of human blood mononuclear cells with chondrocytes, synovial cells, and fibroblasts, Arthritis & Rheumatism, vol.100, issue.12, pp.1372-1381, 1987.
DOI : 10.1002/art.1780301208

H. Cheung and D. Mccarty, Mechanism of connective tissue damage by crystals containing calcium, Rheum Dis Clin North Am, vol.14, pp.365-376, 1988.

H. Cheung, Calcium crystal effects on the cells of the joint: implications for pathogenesis of disease, Current Opinion in Rheumatology, vol.12, issue.3, pp.223-227, 2000.
DOI : 10.1097/00002281-200005000-00012

C. Melchiorri, R. Meliconi, L. Frizzeiero, T. Sylvestri, L. Pulsatelli et al., Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis, Arthritis & Rheumatism, vol.40, issue.12, pp.2165-2174, 1998.
DOI : 10.1002/1529-0131(199812)41:12<2165::AID-ART11>3.0.CO;2-O

S. Abramson, M. Attur, A. Amin, and R. Clancy, Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis, Current Rheumatology Reports, vol.85, issue.6, pp.535-541, 2001.
DOI : 10.1007/s11926-001-0069-3

M. Lotz, THE ROLE OF NITRIC OXIDE IN ARTICULAR CARTILAGE DAMAGE, Rheumatic Disease Clinics of North America, vol.25, issue.2, pp.269-281, 1999.
DOI : 10.1016/S0889-857X(05)70067-3

R. Clancy, J. Rediske, C. Koehne, D. Stoyanovsky, A. Amin et al., Activation of stress-activated protein kinase in osteoarthritic cartilage: evidence for nitric oxide dependence, Osteoarthritis and Cartilage, vol.9, issue.4, pp.294-299, 2001.
DOI : 10.1053/joca.2000.0388

K. Nishida, T. Doi, M. Matsuo, Y. Ishiwari, H. Tsujigiwa et al., Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte formation, Osteoarthritis and Cartilage, vol.9, issue.3, pp.232-237, 2001.
DOI : 10.1053/joca.2000.0380

A. Amin, D. Cesare, P. Attur, M. Tzeng, E. Billard et al., The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase, Journal of Experimental Medicine, vol.182, issue.6, pp.2097-102, 1995.
DOI : 10.1084/jem.182.6.2097

J. Pelletier, D. Jovanovic, J. Fernandes, P. Manning, J. Connor et al., Reduced progression of experimental osteoarthritis in vivo by selective inhibition of inducible nitric oxide synthase, Arthritis & Rheumatism, vol.70, issue.7, pp.1275-1286, 1998.
DOI : 10.1002/1529-0131(199807)41:7<1275::AID-ART19>3.0.CO;2-T

J. Pelletier, D. Jovanovic, J. Fernandes, P. Manning, J. Connor et al., Reduction in the structural changes of experimental osteoarthritis by a nitric oxide inhibitor, Osteoarthritis and Cartilage, vol.7, issue.4, pp.416-418, 1999.
DOI : 10.1053/joca.1998.0229

J. Pelletier, D. Jovanovic, V. Lascau-coman, J. Fernandes, P. Manning et al., Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: Possible link with the reduction in chondrocyte apoptosis and caspase 3 level, Arthritis & Rheumatism, vol.43, issue.6, pp.1290-1299, 2000.
DOI : 10.1002/1529-0131(200006)43:6<1290::AID-ANR11>3.0.CO;2-R

F. Prudhommeaux, C. Schiltz, F. Lioté, A. Hina, R. Champy et al., Variation in the inflammatory properties of basic calcium phosphate crystals according to crystal type, Arthritis & Rheumatism, vol.10, issue.8, pp.1319-1326, 1996.
DOI : 10.1002/art.1780390809

F. Prudhommeaux, A. Meunier, C. Rey, and T. Bardin, Inflammatory potential of in vivo aged basic calcium phosphate crystals, Bioceramics, vol.11, pp.387-390, 1998.

D. Mccarty, J. Lehr, and P. Halverson, Crystal populations in human synovial fluid. Identification of Apatite, Octacalcium Phosphate, and Tricalcium Phosphate, Arthritis & Rheumatism, vol.60, issue.10, pp.1220-1224, 1983.
DOI : 10.1002/art.1780261008

K. Kuettner, B. Pauli, G. Gall, V. Memoli, and R. Schenk, Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology, The Journal of Cell Biology, vol.93, issue.3, pp.743-750, 1982.
DOI : 10.1083/jcb.93.3.743

R. Liu, F. Lioté, D. Rose, D. Merz, and R. Terkeltaub, Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes, Arthritis & Rheumatism, vol.46, issue.Suppl, pp.247-258, 2004.
DOI : 10.1002/art.11486

A. Reginato, R. Iozzo, and S. Jimenez, Formation of nodular structures resembling mature articular cartilage in long???term primary cultures of human fetal epiphyseal chondrocytes on a hydrogel substrate, Arthritis & Rheumatism, vol.13, issue.9, pp.1338-1349, 1994.
DOI : 10.1002/art.1780370912

C. Rey, M. Shimizu, B. Collins, and M. Glimcher, Resolution-enhanced fourier transform infrared spectroscopy study of the environment of phosphate ions in the early deposits of a solid phase of calcium-phosphate in bone and enamel, and their evolution with age. I: Investigations in thev 4 PO4 domain, Calcified Tissue International, vol.5, issue.1, pp.384-394, 1990.
DOI : 10.1007/BF02554969

M. Bradford, A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding, Ann Biochem, vol.7, pp.248-254, 1976.

H. Adler, B. Frech, M. Thöny, H. Pfister, E. Peterhans et al., Inducible nitric oxide synthase in cattle. Differrential cytokine regulation of nitric oxide synthase in bovine and murine macrophages, J Immunol, vol.154, pp.4710-4718, 1995.

M. Ronzière, S. Roche, J. Gouttenoire, O. Démarteau, D. Herbage et al., Ascorbate modulation of bovine chondrocyte growth, matrix protein gene expression and synthesis in three-dimensional collagen sponges, Biomaterials, vol.24, issue.5, pp.851-861, 2003.
DOI : 10.1016/S0142-9612(02)00418-0

A. Badger, M. Cook, M. Lark, T. Newman-tarr, B. Swift et al., SB 203580 inhibits p38 mitogenactivated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes, J Immunol, vol.161, pp.467-473, 1998.

W. Alwan, P. Dieppe, C. Elson, and J. Bradfield, Hydroxyapatite and urate crystal induced cytokine release by macrophages., Annals of the Rheumatic Diseases, vol.48, issue.6
DOI : 10.1136/ard.48.6.476

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1003791

H. Cheung, P. Mitchell, and W. Pledger, Induction of expression of c-fos and c-mye protooncogenes by basic calcium phosphate crystal: effect of beta-interferon, Cancer Res, vol.49, pp.134-138, 1989.

G. Mccarthy, H. Cheung, S. Abel, and L. Ryan, Basic calcium phosphate crystal-induced collagenase production: role of intracellular crystal dissolution, Osteoarthritis and Cartilage, vol.6, issue.3, pp.205-213, 1998.
DOI : 10.1053/joca.1998.0113

A. Borkowf, H. Cheung, and D. Mccarty, Endocytosis is required for the mitogenic effect of basic calcium phosphate crystals in fibroblasts, Calcified Tissue International, vol.38, issue.3, pp.173-176, 1987.
DOI : 10.1007/BF02555703

R. Terkeltaub, D. Santoro, G. Mandel, and N. Mandel, Serum and plasma inhibit neutrophil stimulation by hydroxyapatite crystals. evidence that serum ??l2-hs glycoprotein is a potent and specific crystal-bound inhibitor, Arthritis & Rheumatism, vol.58, issue.9, pp.1081-1089, 1988.
DOI : 10.1002/art.1780310901

E. Ortiz-bravo, M. Sieck, and H. Schumacher, Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model, Arthritis & Rheumatism, vol.53, issue.9, pp.1274-1285, 1993.
DOI : 10.1002/art.1780360912

C. Forsyth, J. Pulai, and R. Loeser, Fibronectin fragments and blocking antibodies to ?2?1 and ?5?1 integrins stimulate mitogen-activated protein kinase signaling and increase collagenase 3 (matrix metalloproteinase 13) production by human articular chondrocytes, Arthritis & Rheumatism, vol.274, issue.9, pp.2368-2376, 2002.
DOI : 10.1002/art.10502

C. Tan, A. Mui, and S. Dedhar, Integrin-linked Kinase Regulates Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression in an NF-??B-dependent Manner, Journal of Biological Chemistry, vol.277, issue.5, pp.3109-3116, 2002.
DOI : 10.1074/jbc.M108673200

J. Pelletier, V. Lascau-coman, D. Jovanovic, J. Fernandes, P. Manning et al., Selective inhibition of inducible nitric oxide synthase in experimental osteoarthritis is associated with reduction in tissue level of catabolic factors, J Rheumatol, vol.26, pp.2002-2014, 1999.

C. Boileau, M. Martel-pelletier, F. Moldovan, J. Jouzeau, P. Netter et al., The in situ up-regulation of chondrocyte interleukin-1-converting enzyme and interleukin-18 levels in experimental osteoarthritis is mediated by nitric oxide, Arthritis & Rheumatism, vol.43, issue.10, pp.2637-2647, 2002.
DOI : 10.1002/art.10518

G. Murrel, D. Jang, and R. Williams, Nitric Oxide Activates Metalloprotease Enzymes in Articular Cartilage, Biochemical and Biophysical Research Communications, vol.206, issue.1, pp.15-21, 1995.
DOI : 10.1006/bbrc.1995.1003

T. Järvinen, T. Moilanen, T. Järvinen, and E. Moilanen, Nitric oxide mediates interleukin-1 induced inhibition of glycosaminoglycan synthesis in rat articular cartilage, Mediators of Inflammation, vol.4, issue.2, pp.107-111, 1995.
DOI : 10.1155/S0962935195000184

D. Taskiran, M. Stefanovic-racic, H. Georgescu, and C. Evans, Nitric-Oxide Mediates Suppression of Cartilage Proteoglycan Synthesis by Interleukin-1, Biochemical and Biophysical Research Communications, vol.200, issue.1, pp.142-148, 1994.
DOI : 10.1006/bbrc.1994.1426

R. Clancy, S. Abramson, C. Kohne, and J. Rediske, Nitric oxide attenuates cellular hexose monophosphate shunt response to oxidants in articular chondrocytes and acts to promote oxidant injury, Journal of Cellular Physiology, vol.263, issue.2, pp.183-191, 1997.
DOI : 10.1002/(SICI)1097-4652(199708)172:2<183::AID-JCP5>3.0.CO;2-K

Y. Henrotin, S. Zheng, G. Deby, A. Labasse, J. Crielaard et al., Nitric oxide downregulates interleukin-1-stimu- lated IL-6, IL-8, and prostaglandin E 2 production by human chondrocytes, J Rheumatol, vol.25, pp.1595-1601, 1998.

L. Cai, S. Suboc, D. Hogue, D. Fei, and E. Filvaroff, Interleukin 17 induced nitric oxide suppresses matrix synthesis and cartilage from matrix breakdown, J Rheumatol, vol.29, pp.1725-1736, 2002.

A. Amin, M. Attur, R. Patel, G. Thakker, P. Marshall et al., Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide., Journal of Clinical Investigation, vol.99, issue.6, pp.1231-1237, 1997.
DOI : 10.1172/JCI119280

J. Bird, S. May, and M. Bayliss, Nitric oxide inhibits aggrecan degradation in explant cultures of equine articular cartilage, Equine Veterinary Journal, vol.13, issue.Suppl. 2, pp.133-139, 2000.
DOI : 10.2746/042516400777591651

D. Stichtenoth and J. Frölich, Nitric oxide and inflammatory joint diseases, Rheumatology, vol.37, issue.3, pp.246-257, 1998.
DOI : 10.1093/rheumatology/37.3.246

M. Stefanovic-racic, T. Morales, D. Taskiran, L. Mcintyre, and C. Evans, The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures, J Immunol, vol.156, pp.1213-1220, 1996.

J. Pelletier, J. Martel-pelletier, and S. Abramson, Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets, Arthritis & Rheumatism, vol.379, issue.6, pp.1237-1247, 2001.
DOI : 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F

A. Mendes, M. Caramona, A. Carvalho, and M. Lopes, Role of Mitogen-Activated Protein Kinases and Tyrosine Kinases on IL-1-Induced NF-??B Activation and iNOS Expression in Bovine Articular Chondrocytes, Nitric Oxide, vol.6, issue.1, pp.35-44, 2002.
DOI : 10.1006/niox.2001.0378

M. Lapointe and E. Isenovic, Interleukin-1?? Regulation of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Involves the p42/44 and p38 MAPK Signaling Pathways in Cardiac Myocytes, Hypertension, vol.33, issue.1, pp.276-282, 1999.
DOI : 10.1161/01.HYP.33.1.276

J. Finder, J. Petrus, A. Hamilton, R. Villavicencio, B. Pitt et al., Signal transduction pathways of IL-1?-mediated iNOS in pulmonary vascular smooth muscle cells, Am J Physiol Lung Cell Mol Physiol, vol.281, pp.816-823, 2001.

Z. Guan, S. Buckman, L. Springer, and A. Morrison, Both p38??MAPK and JNK/SAPK Pathways Are Important for Induction of Nitric-oxide Synthase by Interleukin-1?? in Rat Glomerular Mesangial Cells, Journal of Biological Chemistry, vol.274, issue.51, pp.36200-36206, 1999.
DOI : 10.1074/jbc.274.51.36200

B. Taylor and D. Geller, MOLECULAR REGULATION OF THE HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE (iNOS) GENE, Shock, vol.13, issue.6, pp.413-424, 2000.
DOI : 10.1097/00024382-200006000-00001

J. Marks-konczalik, S. Chu, and J. Moss, Cytokine-mediated Transcriptional Induction of the Human Inducible Nitric Oxide Synthase Gene Requires Both Activator Protein 1 and Nuclear Factor ??B-binding Sites, Journal of Biological Chemistry, vol.273, issue.35, pp.22201-22208, 1998.
DOI : 10.1074/jbc.273.35.22201