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Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis

机译:基质细胞衍生的因子-1作为骨关节炎和类风湿性关节炎的潜在治疗靶标

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With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.
机译:随着年龄的增长,关节受到慢性炎症过程,导致关节软骨变性。虽然多因素,细胞因子已被证明在这些慢性疾病状态的发病机制中发挥作用。基质细胞衍生的因子1(SDF-1)是趋化因子,其已被证明在整个身体的稳态机制和发育过程中是活性的,例如中间骨形成。 SDF-1在从软骨到骨的过渡中起作用。虽然已被证明是正常发展的一个因素,但还显示出涉及类风湿性关节炎(RA)和骨关节炎(OA)的发病机制。在RA中,已显示SDF-1刺激促炎细胞的募集,以及骨科对滑膜,帮助促进滑膜降解。类似地,在OA中,已显示SDF-1来调节涉及关节软骨的降解的关键蛋白。由于其在退行性关节疾病中的作用,已经研究了SDF-1作为潜在的治疗靶标。动物研究一直采用SDF-1抑制剂,例如AMD3100和T140,以研究它们对衰减退行性关节疾病的影响。这些研究表明,有希望减缓软骨降解的进展,并且可能被用作人类OA和RA的治疗靶标。

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