Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-beta 1 in ovariectomized rats

Objective: To explore the effect of vitamin D on turnover of articular cartilage with ovariectomy (OVX) induced OA, and to investigate transforming growth factor-beta 1 (TGF-beta 1) as a possible underlying mechanism mediated by 1 alpha,25(OH)(2)D-3. Design: Sixty-six rats were randomly allocated into seven groups: sham plus control diet (SHAM+CTL), OVX+CTL diet, sham plus vitamin D-deficient (VDD) diet, OVX+VDD diet, and three groups of ovariectomized rats treated with different doses of 1 alpha,25(OH)(2)D-3. The cartilage erosion and the levels of serum 17 beta-estradiol, 1 alpha,25(OH)(2)D-3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-beta 1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-beta 1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-alpha), 1 alpha,25(OH)(2)D-3, and TGF-beta receptor inhibitor (SB505124) in vitro. Results: Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1 alpha,25(OH)(2)D-3 supplementation, and exacerbated by VDD. The expressions of TGF-beta 1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1 alpha,25(OH)(2)D-3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1 alpha,25(OH)(2)D-3 supplementation. In vitro experiments showed that 1 alpha,25(OH)(2)D-3 increased the TGF-beta 1 expression of TNF-alpha stimulated chondrocytes in a dose-dependent manner. 1 alpha,25(OH)(2)D-3 significantly counteracted the increased CTX-II release due to TNF-alpha stimulation, and this effect was significantly suppressed by SB505124. Conclusion: VDD aggravated cartilage erosion, and 1 alpha,25(OH)(2)D-3 supplementation showed protective effects in OVX-induced OA partly through the TGF-beta 1 pathway. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.National Natural Science Foundation of China [11472017, 11002004]; Beijing New-star Plan of Science and Technology [2010B003]SCI(E)PubMedARTICLE986454119@qq.com; tiankun23@163.com; yuweiwu@bjmu.edu.cn; duguohong1@126.com; candyhuang719@hotmail.com; luckyemail2008@sina.com; liuzj@med.mail.com.cn; schl@bjmu.edu.cn; lenghj@bjmu.edu.cn2345-3532