Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 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-β1 (TGF-β1) as a possible underlying mechanism mediated by 1α,25(OH)2D3.


METHODS
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 1α,25(OH)2D3. The cartilage erosion and the levels of serum 17β-estradiol, 1α,25(OH)2D3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-β1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-β1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-α), 1α,25(OH)2D3, and TGF-β receptor inhibitor (SB505124) in vitro.


RESULTS
Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1α,25(OH)2D3 supplementation, and exacerbated by VDD. The expressions of TGF-β1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1α,25(OH)2D3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1α,25(OH)2D3 supplementation. In vitro experiments showed that 1α,25(OH)2D3 increased the TGF-β1 expression of TNF-α stimulated chondrocytes in a dose-dependent manner. 1α,25(OH)2D3 significantly counteracted the increased CTX-II release due to TNF-α stimulation, and this effect was significantly suppressed by SB505124.


CONCLUSIONS
VDD aggravated cartilage erosion, and 1α,25(OH)2D3 supplementation showed protective effects in OVX-induced OA partly through the TGF-β1 pathway.
Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China. Electronic address: 986454119@qq.com.
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Li
Beijing Key Lab of Spine Diseases, Beijing 100191, China. Electronic address: tiankun23@163.com.
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Niu
2nd Dental Center, Peking University School and Hospital of Stomatology, Beijing 100101, China. Electronic address: yuweiwu@bjmu.edu.cn.
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Wu
Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China. Electronic address: duguohong1@126.com.
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Du
Medical Central Lab, Peking University Third Hospital, Beijing 100191, China. Electronic address: candyhuang719@hotmail.com.
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Huang
Beijing Key Lab of Spine Diseases, Beijing 100191, China. Electronic address: luckyemail2008@sina.com.
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Yin
Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China. Electronic address: liuzj@med.mail.com.cn.
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Liu
Beijing Key Lab of Spine Diseases, Beijing 100191, China. Electronic address: schl@bjmu.edu.cn.
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Song
Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China. Electronic address: lenghj@bjmu.edu.cn.
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Leng
D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D010052:Ovariectomy; D010446:Peptide Fragments / Q000097:blood; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1 / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology*
C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D024043:Collagen Type II; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D004958:Estradiol; D002117:Calcitriol
Articular cartilage degradation; CTX-II; Chondrocytes; Ovariectomized rats; TGF-β1; Vitamin D