Modulation of OPG, RANK and RANKL by human chondrocytes and their implication during osteoarthritis
Modulation of OPG, RANK and RANKL by human chondrocytes and their implication during osteoarthritis
复制标题
DOI：
10.1093/rheumatology/kep300
复制
发表时间：
2009-12-01
期刊：
影响因子：
5.5
通讯作者：
Martel-Pelletier, Johanne
中科院分区：
文献类型：
--
作者：
Tat, Steeve Kwan;Amiable, Nathalie;Martel-Pelletier, Johanne
目标。早期的研究表明护骨素(OPG)、等级和等级配体(RANKL)参与了骨关节炎软骨下骨代谢；然而，很少有研究关注它们对软骨细胞的功能影响。我们比较了OPG、RANK和RANKL在人正常软骨细胞和骨性关节炎软骨细胞上的表达和产生，并评价了一些分解代谢因子对骨性关节炎软骨细胞的调节作用。此外，还研究了OPG和RANKL在分解/合成因子产生中的作用。实时荧光定量聚合酶链式反应检测RANK和RANKL的表达，流式细胞仪检测RANK和RANKL的表达，ELISA法检测OPG的表达。用IL-1β、肿瘤坏死因子-α和前列腺素E(2)治疗后确定这些因子的调节。观察使用可溶性RANKL或OPG-FC(不含肝素结合区的OPG)治疗后的功能结果。OPG、RANK和RANKL由人软骨细胞表达和产生。膜级别仅由分布于整个软骨的骨性关节炎软骨细胞亚群(29%)产生。OPG/RANKL比值显著降低(P=0.05)，RANK/RANKL比值显著降低(P<0.05)。
Objectives. Earlier studies suggest the involvement of osteoprotegerin (OPG), RANK and RANK ligand (RANKL) in OA subchondral bone metabolism; however, few studies have looked at their functional consequences on chondrocytes. We compared the expression/production of OPG, RANK and RANKL on human normal and OA chondrocytes, and evaluated, on OA chondrocytes, their modulation by some catabolic factors. Furthermore, the role of OPG and RANKL on the production of catabolic/anabolic factors was assessed.Methods. Expression was determined using real-time PCR, production of RANK and RANKL by flow cytometry and that of OPG by ELISA. Modulation of these factors was determined upon treatment with IL-1 beta, TNF-alpha and PGE(2). The functional consequences were examined following treatment with soluble RANKL or OPG-Fc (OPG without the heparin-binding domain).Results. OPG, RANK and RANKL were expressed and produced by human chondrocytes. Membranous RANK was produced only by an OA chondrocyte subpopulation (29%) localized throughout the cartilage. The OPG/RANKL ratio was significantly (P=0.05)reduced on the OA chondrocytes, whereas the RANK/RANKL ratio was significantly (P