Inhibition of bone resorption blunts osteoarthritis in mice with high bone remodelling
Inhibition of bone resorption blunts osteoarthritis in mice with high bone remodelling
复制标题
DOI：
10.1136/ard.2009.124586
复制
发表时间：
2010-08-01
影响因子：
27.4
通讯作者：
Cohen-Solal, Martine E.
中科院分区：
文献类型：
--
作者：
Kadri, Abderrahim;Funck-Brentano, Thomas;Cohen-Solal, Martine E.
骨关节炎（OA）是一种以软骨退化和骨损伤为特征的疾病。目的通过研究二膦酸盐对高骨重建小鼠骨关节炎（OA）发生的影响，探讨骨重建在OA中的作用。结果术后6周，Runx 2-Tg小鼠胫骨软骨中表达ADAMTS-4和ADAMTS-5的软骨细胞数量较对照组明显增加（p < 0.05）。Runx 2-Tg小鼠的这种增加高于野生型小鼠，尽管它们的OA评分没有差异（2.5 +/- 0.6 vs 2.4 +/- 0.2，P=NS）。帕米膦酸盐降低Runx 2-Tg小鼠的OA评分，但在野生型同窝小鼠中没有（1.2 +/- 0.5 vs 2.7 +/- 0.4; p < 0.05），但不影响正常工作。结论骨吸收水平影响软骨代谢，抑制骨吸收可能阻止软骨蛋白酶的进展，OA。因此，靶向骨吸收可能为治疗高骨吸收型OA提供了一种方法。
Background Osteoarthritis (OA) is characterised by cartilage degradation and bone lesions. Subchondral bone may be involved in the pathogenesis of cartilage matrix breakdown.Objective To assess the role of bone remodelling in OA by studying the effect of bisphosphonate on OA development in mice with high bone remodelling.Methods 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.Results 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.Conclusions 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.