{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:36:52Z","timestamp":1740105412817,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T00:00:00Z","timestamp":1657411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007279","name":"Shanghai Municipal Health Bureau","doi-asserted-by":"publisher","award":["20174Y0062"],"award-info":[{"award-number":["20174Y0062"]}],"id":[{"id":"10.13039\/501100007279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tympanosclerosis (TS) is a result of long\u2010standing middle ear inflammation characterized by fibroblasts ossification. Fibrosis is the last revertible stage in the progress of middle ear inflammation to TS. It was hypothesized that chronic hypoxia could be modulating fibrosis, which in turn additionally further aggravated hypoxia via decreasing oxygen diffusion. However, the effects of hypoxia on osteoinductive activity of fibroblasts have not been explored. Herein, we purposed to explore the role of hypoxia in osteogenic differentiation of fibroblasts derived from TS. The expression of bone morphogenetic protein\u20102 (BMP\u20102), hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1), and Vimentin in the human surgical specimens of tympansclerosis was investigated by immunofluorescent staining. Furthermore, cultured fibroblasts were stratified into the following study groups: control, 25, 50, and 100\u2009\u03bcM cobaltous chloride (CoCl<jats:sub>2<\/jats:sub>) group. BMP\u20102, as well as HIF\u20101\u03b1 levels of expression were detected via western blotting and immunofluorescence analysis. We found that the expression of BMP\u20102 and HIF\u20101\u03b1 was significantly upregulated in TS tissues and these fibroblasts, which was vimentin positive surrounding sclerotic plaques, were also expressing HIF\u20101\u03b1 positive. The results also demonstrated that CoCl<jats:sub>2<\/jats:sub> treatment increased nuclear HIF\u20101\u03b1 protein level in the fibroblast. Furthermore, treatment with CoCl<jats:sub>2<\/jats:sub> significantly increased BMP\u20102 expression and remarkably elevated alkaline phosphatse activity and the mineralized nodules area. These data illustrate that hypoxia may play an osteogenic role in TS fibroblasts via the elevated expression of a possible osteogenic factor, BMP\u20102.<\/jats:p>","DOI":"10.1002\/cbin.11845","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T06:08:47Z","timestamp":1657519727000},"page":"1423-1432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CoCl<sub>2<\/sub>\u2010simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived from\u00a0tympanosclerosis by upregulating the expression of BMP\u20102"],"prefix":"10.1002","volume":"46","author":[{"given":"Chen","family":"Zhang","sequence":"first","affiliation":[{"name":"ENT Institute and Department of Otolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai 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