Abstract |
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.
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Authors | Xin Lu, Xisheng Weng, Zheng Li, Bo Yang, Jun Qian, Yue Huang |
Journal | Inflammopharmacology
(Inflammopharmacology)
Vol. 30
Issue 3
Pg. 843-853
(Jun 2022)
ISSN: 1568-5608 [Electronic] Switzerland |
PMID | 35441352
(Publication Type: Journal Article)
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Copyright | © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG. |
Chemical References |
- Grem1 protein, mouse
- Intercellular Signaling Peptides and Proteins
- MicroRNAs
- Transforming Growth Factor beta
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Topics |
- Animals
- Apoptosis
- Chondrocytes
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Mice
- MicroRNAs
(genetics)
- Osteoarthritis
(pathology)
- Transforming Growth Factor beta
(metabolism)
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