1. Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism.
- Author
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Thomas Funck-Brentano, Hilène Lin, Eric Hay, Marie-Dominique Ah Kioon, Corinne Schiltz, Didier Hannouche, Rémy Nizard, Frédéric Lioté, Philippe Orcel, Marie-Christine de Vernejoul, and Martine Esther Cohen-Solal
- Subjects
Medicine ,Science - Abstract
Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p
- Published
- 2012
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