Inhibition of microRNA‐27b‐3p relieves osteoarthritis pain via regulation of KDM4B‐dependent DLX5

Abstract

Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and β-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis

“…On the other hand, miR-27b-3p was reported to be highly expressed in both samples collected from OA patients and rat models. Suppression of miR-27b-3p promotes the expression of the osteogenic differentiation markers while inhibiting the expression of the adipogenic differentiation markers, inflammatory factors, cellular senescence of bone marrow mesenchymal stem cells (BMSCs), and alleviating OA pain in rats by demethylation of KDM4B (Lysine demethylase 4B) 78 . These observations may explain our previous finding that the lameness score in donkeys has decreased with the progression of OA 1 .…”

Circulating microRNAs Signature as a promising epigenetic diagnostic biomarker of equine osteoarthritis

“…On the other hand, miR27b-3p was reported to be highly expressed in both samples collected from OA patients and rat models. Suppression of miR-27b-3p promotes the expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, in ammatory factors, cellular senescence of bone marrow mesenchymal stem cells (BMSCs), and alleviating OA pain in rats by demethylation of KDM4B (Lysine demethylase 4B) [79]. These observations may explain our previous nding that lameness score in donkeys has been decreased with the progression of OA [1] Concerning COL10A1 expression level in the current study, it increased in the 2 nd , and 3 rd months with the highest level at the 1 st month after MIA injection, then downregulated at 5 th and 7 th months.…”

DNM3OS/miR-127-5p/CDH11, activates Wnt3a/β-catenin/LEF-1 pathway to form a positive feedback and aggravate spine facet joint osteoarthritis

“…CeRNA XIST/miR-211/CXCR4 have been reported to promote the proliferation of OA chondrocytes and promote apoptosis [ 7 ]. Many studies have confirmed that miRNAs participate in the differentiation regulation of bone marrow mesenchymal stem cells (BMSCs) [ [8] , [9] , [10] ]. One of our previous studies revealed that miR-132-3p, miR-99a, miR-127-5p, and miR-125b-3p play essential roles in the tending induction of rat BMSCs [ 11 ].…”