Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Tomogaoka 7-10-2, Suma-ku, Kobe, Hyogo, 654-0142, Japan.
Mol Biol Rep. 2024 Sep 27;51(1):1018. doi: 10.1007/s11033-024-09955-y.
Moderate mechanical stress generated by normal joint loading and movements helps maintain the health of articular cartilage. Despite growing interest in the pathogenesis of cartilage degeneration caused by reduced mechanical stress, its reversibility by mechanical reloading is less understood. This study aimed to investigate the response of articular cartilage exposed to mechanical reloading after unloading in vivo and in vitro.
Disuse atrophy was induced in the knee joint cartilage of adult mice through hindlimb unloading by tail suspension. For in vivo experiments, mice were subjected to reloading with or without daily exercise intervention or surgical destabilization of the knee joint. Microcomputed tomography and histomorphometric analyses were performed on the harvested knee joints. Matrix loss and thinning of articular cartilage due to unloading were fully or partially restored by reloading, and exercise intervention enhanced the restoration. Subchondral bone density decreased by unloading and increased to above-normal levels by reloading. The severity of cartilage damage caused by joint instability was not different even with prior non-weight bearing. For in vitro experiments, articular chondrocytes isolated from the healthy or unloaded joints of the mice were embedded in agarose gel. After dynamic compression loading, the expression levels of anabolic (Sox9, Col2a1, and Acan) and catabolic (Mmp13 and Adamts5) factors of cartilage were analyzed. In chondrocytes isolated from the unloaded joints, similar to those from healthy joints, dynamic compression increased the expression of anabolic factors but suppressed the expression of catabolic factors.
The results of this study indicate that the morphological changes in articular cartilage exposed to mechanical unloading may be restored in response to mechanical reloading by shifting extracellular matrix metabolism in chondrocytes to anabolism.
正常关节负荷和运动产生的适度机械应力有助于维持关节软骨的健康。尽管人们对因机械应力减少而导致的软骨退变的发病机制越来越感兴趣，但对其通过机械再加载的可逆性知之甚少。本研究旨在研究体内和体外在去负荷后暴露于机械再加载的关节软骨的反应。
通过尾吊使成年小鼠的膝关节软骨失用性萎缩。对于体内实验，对小鼠进行再加载，或在再加载的同时进行日常运动干预或膝关节手术不稳定。对收获的膝关节进行微计算机断层扫描和组织形态计量学分析。由于去负荷导致的基质丢失和关节软骨变薄通过再加载得到了完全或部分恢复，而运动干预增强了恢复。去负荷导致的软骨下骨密度降低，通过再加载增加到高于正常水平。即使没有先前的非负重，关节不稳定引起的软骨损伤的严重程度也没有差异。对于体外实验，从小鼠的健康或去负荷关节分离关节软骨细胞，将其嵌入琼脂糖凝胶中。在动态压缩加载后，分析软骨的合成代谢（Sox9、Col2a1 和 Acan）和分解代谢（Mmp13 和 Adamts5）因子的表达水平。在来自去负荷关节的软骨细胞中，与来自健康关节的软骨细胞相似，动态压缩增加了合成代谢因子的表达，但抑制了分解代谢因子的表达。
本研究结果表明，关节软骨暴露于机械去负荷后，细胞外基质代谢向合成代谢转移，可能会恢复其形态变化。
