摘要
雌激素和尼古丁是2种对骨关节炎发病有影响的重要因素,但其影响的具体分子机制仍然存在争议。本研究旨在探讨这2种因素单独和叠加对软骨细胞代谢的影响,从而为骨关节炎的发病机制研究提供一定的参考。鼠胚胎瘤来源的软骨前体细胞系ATDC5在进行铁硒传递蛋白ITS定向诱导能够分化为软骨细胞。研究中对诱导后获得的软骨细胞用雌激素及尼古丁进行了处理。处理后细胞胞外基质蛋白聚糖和二型胶原表达水平分别用甲苯胺蓝染色和免疫组化进行检测,蛋白表达水平和mRNA水平分别进行了Western blot和Real-time PCR验证。研究结果显示尼古丁会造成软骨细胞2种胞外基质分泌的降低,并且促进分解酶MMP13的表达,抑制合成相关蛋白BMP-7的表达。而雌激素能够通过抑制分解酶MMP13和促进基质合成相关蛋白BMP-7的表达来挽回尼古丁对软骨细胞胞外基质的破坏作用。但在mRNA水平,与仅用尼古丁处理相比,雌激素会同时促进mmp13和bmp-7的表达,推测是因为雌激素增强了细胞的代谢效率。这些结果表明,雌激素对受到尼古丁影响的软骨细胞具有保护作用,这可能是骨关节炎初期防治的一个潜在治疗方案。
Estrogen and nicotine are two important factors affecting the pathogenesis of osteoarthritis,but the specific molecular mechanisms of their effects remain controversial.The aim of this study was to investigate the effects of these two factors on the metabolism of chondrocytes alone and in combination,thus providing a reference for the initial prevention and treatment of osteoarthritis.Mouse embryonic progenitor-derived cartilage precursor cell line ATDC5 was selected to be induced by ITS to obtain chondrocyte material.In the experiment,we treated the induced chondrocytes with estrogen and nicotine.After treatment,the expression levels of extracellular matrix proteoglycan and typeⅡ collagen were detected by toluidine blue staining and immunohistochemistry,respectively.The protein expression level and mRNA level were verified by Western blot and Real-time PCR.The results showed that estrogen can restore the destruction of extracellular matrix of chondrocytes by inhibiting the decomposition enzyme MMP13 and promoting the expression of matrix synthesis related protein BMP-7.However,at the mRNA level,estrogen promotes both mmp 13 and bmp -7 expression compared to nicotine treatment alone,possibly because estrogen enhances the metabolic efficiency of the cells.These results show that estrogen has a protective effect on nicotine-affected chondrocytes,which may be a potential treatment for the initial prevention and treatment of osteoarthritis.
作者
彭笑芸
乔之光
王朝霞
PENG Xiao-yun;QIAO Zhi-guang;WANG Zhao-xia(School of Life-Science & Biotechnology,Shanghai Jiaotong University,Shanghai 200240,China;Shanghai Key Laboratory of Orthopaedic Implants/Department of Orthopaedics,Ninth People’s Hospital, School of Medicine,Shanghai Jiaotong University,Shanghai 200011,China;Laboratory Animal Center of Instrumental Analysis Center,Shanghai Jiaotong University,Shanghai 200240,China)
出处
《上海交通大学学报（农业科学版）》
2019年第2期47-53,58,共8页
Journal of Shanghai Jiaotong University(Agricultural Science)
基金
国家自然科学基金青年项目(81701725)
上海市卫生系统重大疾病联合研究项目(2013ZYJB0501)
SMC晨星青年学者奖励计划(AF4040017)
