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

Abstract

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 current study set out to explore the involvement of lncRNA H19 in OA. Methods Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues 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 factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent 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 inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607.

Dihydrocaffeic acid improves IL-1β-induced inflammation and cartilage degradation via inhibiting NF-κB and MAPK signalling pathways

“…Excessive pro-inflammatory factors will trigger the upregulation of catabolic enzymes and downregulation of anabolic enzymes in chondrocytes, and ultimately contribute to the degradation of ECM, the deterioration of cartilage, and the occurrence of OA. [58][59][60] Our in vitro experiments confirmed that DHCA maintains the metabolic balance of chondrocytes by inhibiting inflammatory response. In addition, DMM method was a commonly used surgical strategy for establishing the OA cartilage.…”

Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis

“…The long intergenic non-coding RNA, a regulator of reprogramming (linc-ROR), promotes mesenchymal stem cells’ chondrogenesis and cartilage formation via regulating Sox9 expression [ 42 ]. The upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating tumor protein p53 (TP53), IL-38, and by activating IL-36R [ 43 ]. A recent study also demonstrates that Sox9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation [ 36 ].…”

Identification and verification of ferroptosis‐related genes in diabetic foot using bioinformatics analysis

“…Mutant TP53 can promote the development of inflammation by inhibiting secretory interleukin (IL)-1 receptor antagonists. 46 In addition, early TP53 mutation could promote NF-kB activation in the intestinal organs of mice, inducing severe chronic inflammation and continuous tissue damage in mice, thereby enhancing the predisposition to inflammationrelated colon cancer. 47 TP53 can reportedly reduce the production of inflammatory factors by regulating gene expression in inflammation-related signalling pathways.…”

“…However, studies have found that TP53 is closely related to non‐neoplastic diseases, such as inflammation and blood glucose regulation, in addition to cancer. Mutant TP53 can promote the development of inflammation by inhibiting secretory interleukin (IL)‐1 receptor antagonists 46 . In addition, early TP53 mutation could promote NF‐kB activation in the intestinal organs of mice, inducing severe chronic inflammation and continuous tissue damage in mice, thereby enhancing the predisposition to inflammation‐related colon cancer 47 .…”