Long noncoding RNA H19 alleviates inflammation in osteoarthritis through interactions between TP53, IL-38, and IL-36 receptor

Aims Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the cur-rent study set out to explore the involvement of lncRNA H19 in OA. Methods Firstly, OA mouse models and interleukin (IL)- 1 beta-induced mouse chondrocytes were established. Expression patterns of IL -38 were determined in the synovial fluid and cartilage tis-sues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL -38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain-and loss - of-function assays, the levels of cartilage damage and proinflammatory fac-tors were further detected using safranin O -fast green staining and enzyme-linked immuno-sorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick -End Labeling (TUNEL) in vitro. Results IL -38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL -38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19 -mediated upregulation of IL -38. Furthermore, it was found that the anti-inflammatory effects of IL -38 were achieved by its binding with the IL -36 receptor (IL -36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL -38 or TP53. Conclusion Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflamma-tion and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL -38, and by activating IL -36R.