The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries.
The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries.
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DOI：
10.1177/1947603513495889
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发表时间：
2013-10-01
期刊：
影响因子：
2.8
通讯作者：
Martin JA
中科院分区：
文献类型：
--
作者：
Buckwalter JA;Anderson DD;Brown TD;Tochigi Y;Martin JA
过度的关节表面负荷，无论是单一的（急性冲击事件）或重复的（累积接触应力），可导致骨关节炎（OA）的临床综合征。尽管在治疗关节损伤方面取得了进展，但在过去的50年里，关节损伤后OA的风险并未降低。导致OA的累积过度关节面接触应力由创伤后关节不协调和不稳定以及关节发育不良引起，但也可能导致无已知关节异常的患者发生OA。体外研究表明，过度的关节软骨负荷触发线粒体释放活性氧（ROS），这些ROS导致软骨细胞死亡和基质降解。防止活性氧的释放或抑制其作用可以保护软骨细胞及其基质。从关节软骨中释放的纤维连接蛋白片段也会刺激基质降解;抑制这些片段引发的分子途径可以防止这种效应。此外，受损的软骨细胞释放alarmin，其在体外激活软骨祖细胞，所述软骨祖细胞增殖并迁移到受损软骨的区域。这些细胞还释放趋化因子和细胞因子，可能有助于炎症，导致进行性软骨损失。骨关节炎患者踝关节的牵引和运动可以促进终末期创伤后OA患者的关节重塑，减轻疼痛，改善关节功能。这些进展的理解如何改变机械应力可以导致骨关节炎关节的重塑和过度应力如何导致关节软骨损失，包括识别机械诱导的介质的软骨损失，提供了新的生物和机械方法的基础上，以预防和治疗OA。
Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this effect. Additionally, injured chondrocytes release alarmins that activate chondroprogentior cells in vitro that propogate and migrate to regions of damaged cartilage. These cells also release chemokines and cytokines that may contribute to inflammation that causes progressive cartilage loss. Distraction and motion of osteoarthritic human ankles can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA. These advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA.
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影响因子：
5
作者：
DAVIS, MA;ETTINGER, WH;HAUCK, WW
通讯作者：
HAUCK, WW
影响因子：
2.8
作者：
Anderson, Donald D.;Van Hofwegen, Christopher;Marsh, J. Lawrence;Brown, Thomas D.
通讯作者：
Brown, Thomas D.
影响因子：
6.3
作者：
CROFT, P;COOPER, C;COGGON, D
通讯作者：
COGGON, D
DOI：
10.1073/pnas.97.19.10526
发表时间：
2000-09-12
影响因子：
11.1
作者：
Brines, ML;Ghezzi, P;Cerami, A
通讯作者：
Cerami, A
DOI：
10.1177/107110079301400201
发表时间：
1993-02-01
期刊：
FOOT & ANKLE
影响因子：
--
作者：
BONAR, SK;MARSH, JL
通讯作者：
MARSH, JL