targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism针对osteopenic老鼠和调节骨缓解骨关节炎软骨分解代谢.pdf

Targeting Bone Alleviates Osteoarthritis in Osteopenic Mice and Modulates Cartilage Catabolism 1 ` 1 1 1 1 Thomas Funck-Brentano , Hilene Lin , Eric Hay , Marie-Dominique Ah Kioon , Corinne Schiltz , Didier 2 ´ 2 ´ ´ ´ 1 3 1 Hannouche , Remy Nizard , Frederic Liote , Philippe Orcel , Marie-Christine de Vernejoul , Martine Esther Cohen-Solal1* ´ ˆ ` 1 INSERM U606, Centre Viggo Petersen and Universite Paris-Diderot Paris 7, Hopital Lariboisiere, Paris, France, 2 Department of Orthopedics, Centre Viggo Petersen and ´ ˆ ` ´ ˆ Universite Paris-Diderot Paris 7, Hopital Lariboisiere, Paris, France, 3 Department of Rheumatology, Centre Viggo Petersen and Universite Paris-Diderot Paris 7, Hopital ` Lariboisiere, Paris, France Abstract Objective: 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. Methods: 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 involvemen