MiR-20a-5p facilitates cartilage repair in osteoarthritis via suppressing mitogen-activated protein kinase kinase kinase 2

Abstract

Bone marrow mesenchymal stem cell (BMSC) chondrogenic differentiation contributes to the treatment of osteoarthritis (OA). Numerous studies have indicated that microRNAs (miRNAs) regulate the pathogenesis and development of multiple disorders, including OA. Nevertheless, the role of miR-20a-5p in OA remains obscure. Forty male C57BL/6 mice were divided into four groups and were surgically induced OA or underwent sham surgery in the presence or absence of miR-20a-5p. Flow cytometry was implemented to detect surface markers of BMSCs. Reverse transcription quantitative polymerase chain reaction revealed the upregulation of miR-20a-5p during BMSC chondrogenic differentiation. Western blotting displayed that miR-20a-5p inhibition decreased protein levels of cartilage matrix markers but enhanced those of catabolic and hypertrophic chondrocyte markers in BMSCs. Alcian blue staining, hematoxylin‑eosin staining and micro-CT revealed that miR-20a-5p inhibition restrained chondrogenic differentiation and miR-20a-5p overexpression promoted the repair of damaged cartilage and subchondral bone, respectively. Luciferase reporter assay identified that mitogen activated protein kinase kinase kinase 2 (Map3k2) was a target of miR-20a-5p in BMSCs. Moreover, the expression of miR-20a-5p and Map3k2 was negatively correlated in murine cartilage tissues. Knocking down Map3k2 could rescue the suppressive influence of miR-20a-5p inhibition on chondrogenic differentiation of BMSCs. In conclusion, miR-20a-5p facilitates BMSC chondrogenic differentiation and contributes to cartilage repair in OA by suppressing Map3k2.

Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity

“…MiR-20a-5p promotes the repair of cartilage in osteoarthritis. 15 After treating rat MCLs locoregionally, the upregulated mRNAs noted in MCLs treated with CRX-527 exosomes were found to be statistically significantly enriched in miR-20a-5p targets as compared to MCLs treated with native MSC exosomes. Although the specific contribution of miR-20a-5p to ligament healing remains largely unknown, a decrease in miR-20a-5p levels within CRX-527-exosomes, together with an increase in its target mRNAs in rat ligaments, indicates a potentially negative effect of CRX-527 primed MSC-exosome treatments for ligament healing.…”

microRNAs are differentially expressed in equine plasma of horses with osteoarthritis and osteochondritis dissecans versus control horses

“…Possible explanations for the discrepancy in techniques were previously discussed. Previous studies have shown miR-20a to be elevated in OA cartilage tissues and synovial tissues [25][26][27][28]. miR-20a inhibition led to a reduction of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway activity and chondrocyte apoptosis [28].…”

Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration

“…This drug delivery system induced the osteogenic differentiation of hMSCs by releasing miRNA-20a and siRNA against noggin, which is a BMP antagonist ( Rai et al, 2022 ). miRNA-20a has been shown to enhance osteogenic differentiation of hMSCs by inhibiting the expression of peroxisome proliferator-activated receptor, Bambi, and Crim1, which negatively affects BMP signaling in osteogenesis ( Liu et al, 2022 ). The drug delivery system could increase the release rate of RNA under ultraviolet light, but RNA continued to be released in the absence of ultraviolet light, which necessitates accurate release.…”