Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
Best Pract Res Clin Rheumatol. 2010 Aug;24(4):489-96. doi: 10.1016/j.berh.2010.03.001.
The spectrum of arthritis ranges from erosive (e.g., rheumatoid arthritis) to ossifying disease with formation of new bone (e.g., ankylosing spondylitis and osteoarthritis). The molecular basis for these different patterns of arthritis had long been unclear. In the last few years, however, characterisation of catabolic and anabolic molecular pathways in different forms of arthritis led to a better understanding of joint remodelling and revealed novel therapeutic targets. Recent findings show that catabolic and anabolic molecular pathways govern bone and cartilage remodelling in healthy and arthritic joints. The predominance of catabolic molecular pathways (e.g., receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK and cathepsin K) causes erosive disease whereas anabolic signalling (e.g., Wnt and fibroblast growth factor (FGF)18) favours the formation of new bone including bony spurs and subchondral sclerosis. Other pathways may have a dual function in arthritis (e.g., hedgehog) leading to either catabolic or anabolic joint remodelling dependent on other factors. Key mediators within these signalling pathways may serve as novel targets for treating pathological remodelling of bone and cartilage in arthritis. Molecular pathways govern remodelling processes of bone and cartilage in arthritic joints. Future therapies will likely target the pathologic activity of these molecular pathways to specifically block either catabolic or anabolic joint remodelling in arthritis.
关节炎的范围从侵蚀性（例如类风湿关节炎）到骨形成性疾病（例如强直性脊柱炎和骨关节炎）。这些不同类型关节炎的分子基础长期以来一直不清楚。然而，在过去的几年中，对不同类型关节炎中分解代谢和合成代谢分子途径的特征描述，使人们对关节重塑有了更好的理解，并揭示了新的治疗靶点。最近的发现表明，分解代谢和合成代谢分子途径控制着健康和关节炎关节中的骨和软骨重塑。分解代谢分子途径（例如核因子-κB 受体激活剂配体（RANKL）/RANK 和组织蛋白酶 K）的优势导致侵蚀性疾病，而合成代谢信号（例如 Wnt 和成纤维细胞生长因子（FGF）18）有利于新骨的形成，包括骨赘和软骨下硬化。其他途径在关节炎中可能具有双重功能（例如刺猬），导致依赖于其他因素的分解代谢或合成代谢关节重塑。这些信号通路中的关键介质可作为治疗关节炎中骨和软骨病理性重塑的新靶点。分子途径控制关节炎关节中骨和软骨的重塑过程。未来的治疗方法可能会针对这些分子途径的病理活性，以特异性阻断关节炎中的分解代谢或合成代谢关节重塑。
