MiR-140-3p Ameliorates the Progression of Osteoarthritis <i>via</i> Targeting CXCR4

Abstract

Osteoarthritis is a common disease character with progressive destruction of cartilage. MiR-140-3p was validated as a biomarker for osteoarthritis. However, the mechanism by which miRNA-140-3p regulates osteoarthritis remains unclear. Thus, this study aims to evaluate the potential function of miRNA-140-3p during the pathogenesis of osteoarthritis. MiRNA-140-3p expression in tissue and CHON-001 chondrocyte cells was determined with qRT-PCR. In vitro osteoarthritis model was established by treatment of the chondrocyte cells CHON-001 with IL-1β. Cell proliferation and apoptosis were measured with CCK8 and Annexin V/PI apoptosis assay, respectively. Protein expressions were evaluated using western blot. The target gene of miR-140-3p was predicted using Targetscan and miRDB. MiR-140-3p was downregulated in knee tissue from patients with osteoarthritis. IL-1β inhibited the proliferation of CHON-001 cells via inducing apoptosis. In addition, IL-1β significantly inhibited the expressions of collagen II and aggrecan and increased the level of MMP13. However, the effects of IL-1β could be ameliorated by the addition of miR-140-3p mimics. Moreover, luciferase reporter assay demonstrated CXCR4 as a target gene of miR-140-3p. IL-1β-induced upregulation of CXCR4 could be blocked by miR-140-3p mimics. Our study indicated that miR-140-3p could suppress the progression of osteoarthritis by directly targeting CXCR4. Therefore, miR-140-3p might serve as a potential therapeutic target for the treatment of osteoarthritis.

Circular RNA CSNK1G1 promotes the progression of osteoarthritis by targeting the miR‑4428/FUT2 axis

“…circRNAs function as miRNA sponges that can inhibit the role of miRNAs in restraining targeted expression (10). Previous studies have demonstrated that miRNAs, such as miR-142-5p (11), miR-1202 (12) and miR-140-3p (13) regulate the development of OA by targeting various genes and pathways. Thus, the circRNA/miRNA axis may regulate the progression of OA and may thus present a novel treatment target.…”

Comprehensive Pan-Cancer Analysis of the Prognostic and Immunological Roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C Axis

“…In hepatocellular carcinoma, miR-513b-5p inhibits PIK3R3 expression and represses autophagy ( Jin et al, 2021 ). Huang et al found that miR-140-3p inhibits the progression of osteoarthritis by regulating the expression of CXCR4 ( Ren et al, 2020 ). Koike et al reported that miR-140 regulated the expression of NF-κB coactivators, which resulted in the suppression of NF-κB activity ( Takata et al, 2011 ).…”

Recent progress on the role of miR-140 in cartilage matrix remodelling and its implications for osteoarthritis treatment

“…Beyond miR-140 targets in the cartilage matrix, several studies have identified other targets in endochondral bone development, including bone morphogenic protein (BMP)-2 [38], DNPEP [32], and transforming growth factor beta receptor (TGFBR) 1 [40]. In comparison to the number of miR-140-5p targets, fewer miR-140-3p targets have been identified, including CXCR4, which is associated with in OA progression [35], and RAS-like proto-oncogene A (RALA), which is associated with MSC chondrogenesis [36].…”