Fang Jie, Xiao Li, Chen Rebecca, Zhao Zhihe
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, United States of America.
PLoS One. 2017 May 18;12(5):e0177826. doi: 10.1371/journal.pone.0177826. eCollection 2017.
Recent emerging data indicate that the increase in the expression and activity of the transforming growth factor beta 1 (Tgf-β1) signaling may have detrimental effect to mature articular cartilage of knee joints. However, there is no information about whether or not this is the case in condylar cartilages. The objective of this study is to investigate the protein expression and activity of Tgf-β1 signaling in degenerative condylar cartilages. We also investigate biological effects of the conditional deletion of transforming growth factor receptor type II (Tgfbr2) in condylar cartilage of adult mice after a partial discectomy. Two mouse models of osteoarthritis (OA) were used to examine protein expressions of Tgf-β1 and p-Smad2/3 in condylar cartilages at early degenerative stages. In addition, cartilage specific Tgfbr2-deficient adult mice were subjected to a partial discectomy. The morphological condition of condylar cartilages was evaluated in mice at 4 and 12 weeks after the surgery. We found that protein levels of Tgf-β1 and p-Smad2/3 were increased in the degenerative condylar cartilage of the mouse models. The conditional removal of Tgfbr2 in mature condylar cartilage significantly delayed the progressive progression of the cartilage degeneration induced by a partial discectomy. We conclude that the increase in the expression and activity of Tgf-β1 signaling may have detrimental effect to mature condylar cartilages. Therefore, inhibition of Tgf-β1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints.
最近出现的数据表明,转化生长因子β1(Tgf-β1)信号传导的表达和活性增加可能会对膝关节的成熟关节软骨产生有害影响。然而,关于髁突软骨是否也是这种情况尚无相关信息。本研究的目的是调查退变髁突软骨中Tgf-β1信号传导的蛋白表达和活性。我们还研究了成年小鼠部分椎间盘切除术后,髁突软骨中条件性缺失转化生长因子Ⅱ型受体(Tgfbr2)的生物学效应。使用两种骨关节炎(OA)小鼠模型来检测早期退变阶段髁突软骨中Tgf-β1和p-Smad2/3的蛋白表达。此外,对软骨特异性Tgfbr2缺陷的成年小鼠进行部分椎间盘切除术。在术后4周和12周评估小鼠髁突软骨的形态状况。我们发现,在小鼠模型的退变髁突软骨中,Tgf-β1和p-Smad2/3的蛋白水平升高。在成熟髁突软骨中条件性去除Tgfbr2可显著延缓部分椎间盘切除术诱导的软骨退变的进展。我们得出结论,Tgf-β1信号传导的表达和活性增加可能会对成熟髁突软骨产生有害影响。因此,抑制Tgf-β1信号传导可能能够保护成熟颞下颌关节中的髁突软骨不被降解。