Department of Immunology, Institute of Microbiology, Sofia, Bulgaria.
Rheumatol Int. 2012 May;32(5):1317-25. doi: 10.1007/s00296-010-1723-8. Epub 2011 Feb 3.
Joint destruction and excessive bone formation are associated with high expression of soluble receptor activator of nuclear factor-κB ligand (sRANKL). This study was undertaken to investigate the role of sRANKL in collagenase-induced osteoarthritis (CIOA) in mice and in patients with osteoarthritis (OA). The initial phase of CIOA was associated with severe proteoglycan depletion, decreased collagen density, and up-regulation of bone morphogenetic protein (BMP)-2. At the late stage of CIOA, bone remodeling was related with increased BMP2 and RANKL expression in the joints, high sRANKL, and decreased number of activated neutrophils in synovium. CIOA mice showed elevated plasma level of sRANKL but low RANKL expression on blood neutrophils. The percentage of RANKL-positive blood neutrophils was higher in patients with OA than in healthy individuals. Our data indicate that increased local and systemic levels of soluble RANKL might be indicative for OA disorders in mouse and human.
关节破坏和过度骨形成与可溶核因子-κB 配体受体激活剂（sRANKL）的高表达有关。本研究旨在探讨 sRANKL 在胶原酶诱导的骨关节炎（CIOA）小鼠和骨关节炎（OA）患者中的作用。CIOA 的初始阶段与严重的蛋白聚糖耗竭、胶原密度降低以及骨形态发生蛋白（BMP）-2 的上调有关。在 CIOA 的晚期阶段，关节中 BMP2 和 RANKL 的表达增加、sRANKL 升高以及滑膜中活化中性粒细胞数量减少与骨重塑有关。CIOA 小鼠表现出血浆 sRANKL 水平升高，但血液中性粒细胞上的 RANKL 表达降低。OA 患者血液中 RANKL 阳性中性粒细胞的百分比高于健康个体。我们的数据表明，局部和全身可溶性 RANKL 水平的升高可能是小鼠和人类 OA 疾病的标志物。
