Choi Yongwon, Arron Joseph R, Townsend Michael J
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Nat Rev Rheumatol. 2009 Oct;5(10):543-8. doi: 10.1038/nrrheum.2009.175.
Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disease that results in inflammation and structural destruction of the joints. A hallmark of RA pathogenesis is an imbalance of the osteoblast-osteoclast axis driven by inflammatory processes, resulting in elevated bone resorption by osteoclasts. Current therapies used to treat this disease have focused on inhibition of synovitis, but such treatments do not adequately repair damaged bone. A key pathway of osteoclast formation involves the receptor activator of nuclear factor kappaB ligand (RANKL) pathway acting on myeloid progenitor cells. The Wnt pathway has been shown to be important for the differentiation of osteoblasts from mesenchymal lineage precursors, and endogenous Wnt inhibitors, such as Dickkopf1 and sclerostin, might have important roles in osteoclast dysregulation in RA. Inhibition of the RANKL pathway, or blockade of Dickkopf1 and sclerostin, might serve to restore the osteoblast-osteoclast balance and repair bone erosion in RA joints. Such treatments, in combination with anti-inflammatory therapies, could stabilize and repair damaged joints and have the potential to be valuable additions to the armory of RA treatments.
类风湿关节炎（RA）是一种慢性、使人衰弱的自身免疫性疾病，会导致关节炎症和结构破坏。RA发病机制的一个标志是由炎症过程驱动的成骨细胞-破骨细胞轴失衡，导致破骨细胞引起的骨吸收增加。目前用于治疗这种疾病的疗法主要集中在抑制滑膜炎，但此类治疗并不能充分修复受损骨骼。破骨细胞形成的一个关键途径涉及作用于髓系祖细胞的核因子κB受体活化因子配体（RANKL）途径。Wnt途径已被证明对间充质谱系前体分化为成骨细胞很重要，而内源性Wnt抑制剂，如Dickkopf1和硬化蛋白，可能在RA的破骨细胞失调中起重要作用。抑制RANKL途径或阻断Dickkopf1和硬化蛋白，可能有助于恢复RA关节中成骨细胞-破骨细胞的平衡并修复骨侵蚀。此类治疗与抗炎疗法相结合，可稳定并修复受损关节，有可能成为RA治疗手段中的宝贵补充。
