Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka Suita, Osaka 565-0871, Japan.
Int J Mol Sci. 2022 Apr 23;23(9):4672. doi: 10.3390/ijms23094672.
Owing to the rapid aging of society, the numbers of patients with joint disease continue to increase. Accordingly, a large number of patients require appropriate treatment for osteoarthritis (OA), the most frequent bone and joint disease. Thought to be caused by the degeneration and destruction of articular cartilage following persistent and excessive mechanical stimulation of the joints, OA can significantly impair patient quality of life with symptoms such as knee pain, lower limb muscle weakness, or difficulty walking. Because articular cartilage has a low self-repair ability and an extremely low proliferative capacity, healing of damaged articular cartilage has not been achieved to date. The current pharmaceutical treatment of OA is limited to the slight alleviation of symptoms (e.g., local injection of hyaluronic acid or non-steroidal anti-inflammatory drugs); hence, the development of effective drugs and regenerative therapies for OA is highly desirable. This review article summarizes findings indicating that proteoglycan 4 ()/lubricin, which is specifically expressed in the superficial zone of articular cartilage and synovium, functions in a protective manner against OA, and covers the transcriptional regulation of in articular chondrocytes. We also focused on growth differentiation factor 5 (, which is specifically expressed on the surface layer of articular cartilage, particularly in the developmental stage, describing its regulatory mechanisms and functions in joint formation and OA pathogenesis. Because several genetic studies in humans and mice indicate the involvement of these genes in the maintenance of articular cartilage homeostasis and the presentation of OA, molecular targeting of and is expected to provide new insights into the aetiology, pathogenesis, and potential treatment of OA.
由于社会的快速老龄化，患有关节疾病的患者人数持续增加。因此，大量患者需要适当的治疗方法来治疗骨关节炎（OA），OA 是最常见的骨骼和关节疾病。OA 被认为是由于关节持续和过度机械刺激导致关节软骨的退化和破坏引起的，它会显著降低患者的生活质量，其症状包括膝关节疼痛、下肢肌肉无力或行走困难等。由于关节软骨自我修复能力低、增殖能力极低，到目前为止，受损的关节软骨还没有得到修复。OA 的当前药物治疗仅限于症状的轻微缓解（例如，局部注射透明质酸或非甾体抗炎药）；因此，开发有效的 OA 药物和再生疗法是非常需要的。这篇综述文章总结了研究结果，表明特异性表达在关节软骨和滑膜浅层的蛋白聚糖 4（）/润滑素以保护作用对抗 OA，并涵盖了关节软骨细胞中 的转录调控。我们还重点介绍了生长分化因子 5（，其特异性表达在关节软骨的表层，特别是在发育阶段，描述了其在关节形成和 OA 发病机制中的调节机制和功能。由于人类和小鼠的几项遗传研究表明这些基因参与维持关节软骨的内稳态和 OA 的发生，因此靶向 和 的分子有望为 OA 的病因、发病机制和潜在治疗提供新的见解。
