INSERM U606, Centre Viggo Petersen and Université Paris-Diderot Paris 7, Hôpital Lariboisière, 2 rue Ambroise Paré, Paris 75010, France.
Ann Rheum Dis. 2010 Aug;69(8):1533-8. doi: 10.1136/ard.2009.124586. Epub 2010 Jun 4.
Osteoarthritis (OA) is characterised by cartilage degradation and bone lesions. Subchondral bone may be involved in the pathogenesis of cartilage matrix breakdown.
To assess the role of bone remodelling in OA by studying the effect of bisphosphonate on OA development in mice with high bone remodelling.
Mice overexpressing Runx2 (Runx2-Tg) under the control of collagen type I that displayed high bone remodelling were used. Joint instability was performed by partial medial meniscectomy to induce OA.
Six weeks after surgery, tibial cartilage of Runx2-Tg mice displayed an increased number of ADAMTS-4- and ADAMTS-5-expressing chondrocytes compared with controls (p<0.05). This increase was higher in Runx2-Tg mice than in wild-type mice, although their OA score did not differ (2.5+/-0.6 vs 2.4+/-0.2, P=NS). Pamidronate reduced the OA score in Runx2-Tg mice but not in wild-type littermates (1.2+/-0.5 vs 2.7+/-0.4; p<0.05) despite the reduction of bone resorption and of the expression of cartilage proteases in both genotypes.
These findings support the hypothesis that the level of bone resorption influences cartilage metabolism and that inhibition might prevent the progression of OA. Targeting bone resorption might therefore provide an approach to the treatment of high bone resorbing forms of OA.
骨关节炎（OA）的特征是软骨降解和骨损伤。软骨下骨可能参与了软骨基质破坏的发病机制。
通过研究双膦酸盐对高骨重塑小鼠 OA 发展的影响，评估骨重塑在 OA 中的作用。
使用在 I 型胶原控制下过表达 Runx2 的小鼠（Runx2-Tg），其表现出高骨重塑。通过部分内侧半月板切除术导致关节不稳定以诱导 OA。
手术后 6 周，Runx2-Tg 小鼠的胫骨软骨中 ADAMTS-4 和 ADAMTS-5 表达的软骨细胞数量增加，与对照组相比（p<0.05）。尽管它们的 OA 评分没有差异（2.5+/-0.6 与 2.4+/-0.2，P=NS），但这种增加在 Runx2-Tg 小鼠中比在野生型小鼠中更高。帕米膦酸盐降低了 Runx2-Tg 小鼠的 OA 评分，但对野生型同窝小鼠没有影响（1.2+/-0.5 与 2.7+/-0.4；p<0.05），尽管两种基因型的骨吸收和软骨蛋白酶表达均减少。
这些发现支持这样一种假设，即骨吸收水平影响软骨代谢，抑制可能会阻止 OA 的进展。因此，靶向骨吸收可能是治疗高骨吸收型 OA 的一种方法。
