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Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross\u2010effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of the study<\/jats:title><jats:p>Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation. Toluidine staining and immunohistochemistry were used to detect the extracellular matrix (ECM) of chondrocytes, while the important proteins in the metabolism of chondrocytes were detected by Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nicotine\u2010induced inflammatory supernatant promoted the degradation of ECM, such as type II collagen, aggrecan and proteoglycan 4. While in the presence of physiological concentrations of estrogen, this destructive effect is reversed. On the molecular level, estrogen (17\u03b2<jats:bold>\u2010<\/jats:bold>estradiol, 1\u00a0nmol\/L) can inhibit the matrix degrading enzymes and promote the transforming growth factor (TGF)\u2010\u03b21 pathway which is involved in matrix synthesis. However, in the presence of inflammatory induction, although estrogen could still inhibit the expression of matrix degrading enzymes, it inhibited the TGF\u2010\u03b21 pathway. Moreover, the different inflammatory factors in the inflammatory supernatant, mainly tumor necrosis factor\u2010\u03b1, interleukin\u20101\u03b2, had different effects on the metabolic processes of chondrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Estrogen reverses nicotine\u2010induced inflammation mainly via reducing the degradation of ECM. The cross\u2010effect of estrogen and inflammatory factor inhibitors can be a potential clinical reference for OA patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13476","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T07:02:22Z","timestamp":1549954942000},"page":"666-676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Estrogen reverses nicotine\u2010induced inflammation in chondrocytes via reducing the degradation of ECM"],"prefix":"10.1111","volume":"22","author":[{"given":"Xiaoyun","family":"Peng","sequence":"first","affiliation":[{"name":"School of Life\u2010Science &amp; Biotechnology Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-3376","authenticated-orcid":false,"given":"Zhiguang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shanghai Key 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