Protective role of microRNA-23a/b-3p inhibition against osteoarthritis through Gremlin1-depenent activation of TGF-β/smad signaling in chondrocytesa

The changed biomechanical environment of chondrocytes elicited by altered extracellular matrix is reported to accelerate the progression of OA. MicroRNAs (miRNAs or miRs) have emerged as major regulators in chondrocyte function. Hence, we explored effect of miR-23a/b-3p on OA in regulating chondrocy...

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Bibliographic Details
Published in:Inflammopharmacology 2022-06, Vol.30 (3), p.843-853
Main Authors: Lu, Xin, Weng, Xisheng, Li, Zheng, Yang, Bo, Qian, Jun, Huang, Yue
Format: Article
Language:English
Subjects:
Allergology
Animals
Apoptosis
Biomedical and Life Sciences
Biomedicine
Chondrocytes
Dermatology
Gastroenterology
Immunology
Mice
MicroRNAs - genetics
Original Article
Osteoarthritis - pathology
Pharmacology/Toxicology
Rheumatology
Transforming Growth Factor beta - metabolism
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Summary:The changed biomechanical environment of chondrocytes elicited by altered extracellular matrix is reported to accelerate the progression of OA. MicroRNAs (miRNAs or miRs) have emerged as major regulators in chondrocyte function. Hence, we explored effect of miR-23a/b-3p on OA in regulating chondrocyte growth. The medial meniscus and anterior cruciate ligaments of right knee was removed to induce a mouse model of OA. miR-23a/b-3p and Gremlin1 (Grem1) expressions in OA were determined by RT-qPCR. Dual luciferase reporter gene assay was conducted to assess their relationship in the context of OA. Loss- and gain-of-function assays were adopted to clarify their effects on OA by determining the release of pro-inflammatory proteins and the apoptosis of chondrocytes. RT-qPCR determined increased miR-23a/b-3p expression and decreased Grem1 expression in the setting OA. Inhibiting miR-23a/b-3p or overexpressing Grem1 activated transforming growth factor-β/solvated metal atom dispersed 3 (TGF-β/Smad) signaling to prevent OA development. Silencing Grem1 ablated suppressive effects of miR-23a/b-3p inhibitor on the release of pro-inflammatory proteins and the apoptosis of chondrocytes. To conclude, inhibition of miR-23a/b-3p delays OA progression through Grem1-mediated activation of TGF-β/Smad signaling, contributing to deepen understanding of the pathogenesis of OA.
ISSN:0925-4692
1568-5608
DOI:10.1007/s10787-022-00923-1