Kaempferol protects chondrogenic ATDC5 cells against inflammatory injury triggered by lipopolysaccharide through down-regulating miR-146a

摘要

Kaempferol is a kind of bioflavonoid exerts diverse pharmacological activities, including anti-apoptotic and anti-inflammatory activities. Kaempferol has been recognized as an effective agent for alleviating the clinical symptoms of osteoarthritis (OA). This study aimed to provide evidence that Kaempferol has potential in the management of OA. Lipopolysaccharide (LPS) stimulation induced a significant cell death and inflammatory injury in ATDC5 cells, as evidenced by the decreased cell viability, the induced apoptosis, the activated caspase-3, and the excessive production of IL-6, IL-8 and TNF-alpha. Precondition of cells with Kaempferol prevented apoptosis and the release of proinflammatory cytokines triggered by LPS. miR-146a was down-regulated by Kaempferol treatment, and Decorin was up-regulated by miR-146a overexpression. Consistently, both silence of miR-146a and Decorin exhibited Kaempferol-like effects towards ATDC5 cells stimulated by LPS. Moreover, Decorin silence activated PI3K/AICT/mTOR signaling pathway. In rat model of OA, the expression of miR-146a and Decorin in cartilage tissues was repressed by Kaempferol. Also, the activated PI3K/AKT/mTOR signaling pathway in OA animal model was enhanced by Kaempferol administration. These data suggested that Kaempferol exerted potential anti-OA effects through down-regulation of miR-146a, and thus repressing the expression of Decorin.