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Oestrogen deficiency modulates particle-induced osteolysis.

Abstract : ABSTRACT: INTRODUCTION: Postmenopausal osteoporosis may modulate bone response to wear debris. In this article, we evaluate the influence of oestrogen deficiency on experimental particle-induced osteolysis. METHODS: Polyethylene (PE) particles were implanted onto the calvaria of normal controls, sham-ovariectomized (OVX), OVX mice and OVX mice supplemented with oestrogen (OVX+E). After 14 days, seven skulls per group were analyzed using a high-resolution micro-computed tomography (micro-CT) and histomorphometry, and for tartrate-specific alkaline phosphatase. Five calvariae per group were cultured for the assay of IL-1β, IL-6, TNF-α and receptor activator of the nuclear factor κB (RANKL) secretion using quantitative ELISA. Serum IL-6 concentrations were obtained. The expression of RANKL and osteoprotegerin (OPG) mRNA were evaluated using real-time PCR. RESULTS: As assessed by μCT and by histomorphometry, PE particles induced extensive bone resorption and an intense inflammatory reaction in normal controls, sham-OVX and OVX+E mice, but not in the OVX mice group. In normal controls, sham-OVX and OVX+E mice, PE particles induced an increase in serum IL-6, in TNF-α and RANKL local concentrations, and resulted in a significant increase in RANKL/OPG messenger RNA (mRNA) ratio. Conversely, these parameters remained unchanged in OVX mice after PE implantation. CONCLUSIONS: Oestrogen privation in the osteolysis murine model ultimately attenuated osteolytic response to PE particles, suggesting a protective effect. This paradoxical phenomenon was associated with a down-regulation of pro-resorptive cytokines. It is hypothesized that excessive inflammatory response was controlled, illustrated by the absence of increase of serum IL-6 in OVX mice after PE implantation.
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Submitted on : Friday, July 29, 2011 - 6:01:00 PM
Last modification on : Thursday, April 9, 2020 - 11:54:38 AM
Long-term archiving on: : Sunday, December 4, 2016 - 2:03:53 PM

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Christophe Nich, Jean Langlois, Arnaud Marchadier, Catherine Vidal, Martine Cohen-Solal, et al.. Oestrogen deficiency modulates particle-induced osteolysis.. Arthritis Research and Therapy, BioMed Central, 2011, 13 (3), pp.R100. ⟨10.1186/ar3381⟩. ⟨inserm-00612683⟩

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