MiR-320a upregulation improves IL-1β-induced osteoarthritis via targeting the DAZAP1 and MAPK pathways

Abstract

Purpose Osteoarthritis (OA), a constant illness described by articular cartilage degeneration, usually manifested by joint pain and helpless development. Numerous literatures suggest that microRNAs play an important regulatory role in OA, yet the role of miR-320a in OA remains largely obscure. Materials and methods To evaluate the expression of miR-320a mRNA, quantitative real-time polymerase chain reaction was used. Cell counting kit-8 assay, Edu staining, Annexin V-FITC/PI apoptosis detection assay, Caspases 3 staining, and trypan staining were conducted to monitor cell proliferation and apoptosis. Western blot was applied to examine DAZAP1 and ERK/JNK/MAPK associated protein expression. Luciferase reporter gene experiments were performed to confirm the relationships between miR-320a and DAZAP1. ELISA assay was adopted to analyze the secretion of inflammation cytokines IL-6, IL-8, and TNF-α. Results In an in vitro osteoarthritis model caused by IL-1β, miR-320a expression was markedly reduced. Overexpression of miR-320a restored IL-1β-inhibited chondrocyte proliferation, induced apoptosis and inflammatory response. Mechanistically, miR-320a affected HC-A cell proliferation, apoptosis and inflammatory response by regulating DAZAPI. Meanwhile, the ERK/JNK/MAPK pathway is also involved in the regulatory role of miR-320a on OA. Conclusion Our results show an important role for miR-320a and provide new therapeutic targets for avoiding and treating osteoarthritis.

A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment

“…Upregulated miR-223-3p inhibited apoptosis and the inflammatory response in chondrocytes induced by IL-1β by directly targeting NLRP3 [51]. By targeting the DAZAP1 and MAPK pathways, upregulated miR-320a improved IL-1β-induced osteoarthritis by enhancing chondrocyte proliferation, reducing apoptosis, and decreasing inflammatory response [52]. The miR-320a also played a role in protecting cartilage against degeneration by regulating the protein expression levels of BMI-1 and RUNX2 in chondrocytes [53].…”

Donor Sites and Harvesting Techniques Affect miRNA Cargos of Extracellular Vesicles Released by Human Adipose-Derived Mesenchymal Stromal Cells

“…In A-ASC-EVs, miR-320a was also upregulated and has been reported in the literature to be important in the regulation of OA, involving the ERK/JNK/MAPK pathway. Indeed, in vitro experiments demonstrated that overexpression of miR-320a restored chondrocyte proliferation inhibited by IL-1β, and reduced apoptosis and inflammatory response [ 43 ].…”