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There is currently no effective treatment that can arrest or reverse OA progression. Kruppel-like factor 2 (KLF2), a member of the zinc finger family, has emerged as a transcription factor involved in a wide variety of inflammatory diseases. Here, we identified that KLF2 expression is downregulated in IL-1<jats:italic>\u03b2<\/jats:italic>-treated human chondrocytes and OA cartilage. Genetic and pharmacological overexpression of KLF2 suppressed IL-1<jats:italic>\u03b2<\/jats:italic>-induced apoptosis and matrix degradation through the suppression of reactive oxygen species (ROS) production. In addition, KLF2 overexpression resulted in increased expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) through the enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further, Nrf2 inhibition abrogated the chondroprotective effects of KLF2. Safranin O\/fast green and TUNEL staining demonstrated that adenovirus-mediated overexpression of KLF2 in joint cartilage protects rats against experimental OA by inhibiting cartilage degradation and chondrocyte apoptosis. Immunohistochemical staining revealed that KLF2 overexpression significantly decreases MMP13 expression caused by OA progression <jats:italic>in vivo<\/jats:italic>. This <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> study is the first to investigate the antioxidative effect and mechanisms of KLF2 in OA pathogenesis. Our results collectively provide new insights into OA pathogenesis regulated by KLF2 and a rationale for the development of effective OA intervention strategies.<\/jats:p>","DOI":"10.1155\/2019\/8564681","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T18:31:14Z","timestamp":1574188274000},"page":"1-18","source":"Crossref","is-referenced-by-count":34,"title":["KLF2 Protects against Osteoarthritis by Repressing Oxidative Response through Activation of Nrf2\/ARE Signaling <i>In Vitro<\/i> and <i>In Vivo<\/i>"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-3464","authenticated-orcid":true,"given":"Xiang","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Hospital of China Medical University, Shenyang 110000, 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