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The aim of this study was to investigate the role of Notch signaling changes during proliferation and differentiation of chondrocyte, and to testify the mechanism of MMP-13 regulation by Notch and Runx2 expression changes during osteoarthritis. In this study, Chondrocytes were isolated from rat knee cartilages. Notch signaling was activated\/inhibited by Jagged-1\/DAPT. Proliferative capacity of Chondrocytes was analyzed by CCK-8 staining and EdU labeling. ColX, Runx2 and MMP-13 expressions were analyzed as cell differentiation makers. Then, Runx2 gene expression was interfered using lentivirus transfection (RNAi) and was over-expressed by plasmids transfected siRNA in chondrocytes, and MMP-13 expression was analyzed after Jagged-1\/DAPT treatment. <jats:italic>In vivo<\/jats:italic>, an intra-articular injection of shRunx2 lentivirus followed with Jagged1\/DAPT treatments was performed in rats. MMP-13 expression in articular cartilage was detected by immunohistochemistry. Finally, MMP-13 expression changes were analyzed in chondrocytes under IL-1\u03b2 stimulation. Our findings showed that, CCK-8 staining and EdU labeling revealed suppression of cell proliferation by Notch signaling activation after Jagged-1 treatment in chondrocytes. Promoted differentiation was also observed, characterized by increased expressions of Col X, MMP-13 and Runx2. Meanwhile, Sox9, aggrecan and Col II expressions were down-regulated. The opposite results were observed in Notch signaling inhibited cells by DAPT treatment. In addition, Runx2 RNAi significantly attenuated the \u2018regulatory sensitivity\u2019 of Notch signaling on MMP-13 expression both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. However, we found there wasn\u2019t significant changes of this \u2018regulatory sensitivity\u2019 of Notch signaling after Runx2 over-expression. Under IL-1\u03b2 circumstance, MMP-13 expression could be reduced by both DAPT treatment and Runx2 RNAi, while Runx2 interference also attenuated the \u2018regulatory sensitivity\u2019 of Notch in MMP-13 under IL-1\u03b2 stimulation. In conclusion, Notch signaling is an important regulator on rat chondrocyte proliferation and differentiation, and this regulatory effect was partially mediated by proper Runx2 expression under both normal and IL-1\u03b2 circumstances. In the meanwhile, DAPT treatment could effectively suppress expression of MMP-13 stimulated by IL-1 \u03b2.<\/jats:p>","DOI":"10.1038\/s41598-019-52125-5","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T20:29:05Z","timestamp":1572467345000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Notch Signaling Regulates MMP-13 Expression via Runx2 in Chondrocytes"],"prefix":"10.1038","volume":"9","author":[{"given":"Di","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiye","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songsong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"52125_CR1","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1053\/berh.2002.0266","volume":"16","author":"IF Petersson","year":"2002","unstructured":"Petersson, I. 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