Related Experiment Video
Updated: Aug 8, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
MicroRNA-146a-5p alleviates the pathogenesis of osteoarthritis by inhibiting SDF-1/CXCR4-induced chondrocyte
Tengyun Yang1, Canzhang Li1, Yanlin Li1
1Department of Sports Medicine, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, Yunnan, China.
Background:
SDF-1/CXCR4 signaling promotes osteoarthritis (OA) development. CXCR4 is a potential target of miR-146a-5p. This study investigated the therapeutic role and the underlying mechanism of miR-146a-5p in OA.
Methods:
Human primary chondrocytes C28/I2 were stimulated with SDF-1. Cell viability and LDH release were examined. Chondrocyte autophagy was assessed using Western blot analysis, ptfLC3 transfection, and transmission electron microscopy. MiR-146a-5p mimics were transfected into C28/I2 cells to investigate the role of miR-146a-5p in SDF-1/CXCR4-induced autophagy of chondrocytes. An SDF-1-induced rabbit OA model was established to investigate the therapeutic role of miR-146a-5p in OA. Histological staining was performed to observe the morphology of osteochondral tissue.
Results:
SDF-1/CXCR4 signaling promoted autophagy in C28/I2 cells, as demonstrated by increased LC3-II protein expression and autophagic flux induced by SDF-1. SDF-1 treatment significantly inhibited cell proliferation while promoting necrosis and autophagosome formation in C28/I2 cells. In the presence of SDF-1, miR-146a-5p overexpression in C28/I2 cells suppressed CXCR4 mRNA expression, LC3-II and Beclin-1 protein expression, LDH release, and autophagic flux. In addition, SDF-1 increased the autophagy of chondrocytes in rabbits and promoted the development of OA. Compared with the negative control, miR-146a-5p significantly reduced the morphological abnormalities of the rabbit cartilage that were induced by SDF-1, as well as the number of LC3-II-positive cells, protein expression of LC3-II and Beclin 1, and mRNA expression of CXCR4 in osteochondral tissue. These effects were reversed by the autophagy agonist rapamycin.
Conclusions:
SDF-1/CXCR4 promotes OA development by enhancing chondrocyte autophagy. MicroRNA-146a-5p may alleviate OA by suppressing CXCR4 mRNA expression and SDF-1/CXCR4-induced chondrocyte autophagy.
Insights
MicroRNA-146a-5p may alleviate osteoarthritis by suppressing SDF-1/CXCR4 signaling and chondrocyte autophagy. This study investigated its therapeutic role in OA development and underlying mechanisms.
Area of Science:
- Molecular Biology
- Cell Biology
- Pathology
Background:
- Osteoarthritis (OA) development is promoted by Stromal cell-Derived Factor 1 (SDF-1)/CXCR4 signaling.
- CXCR4 is a potential molecular target of microRNA-146a-5p (miR-146a-5p).
Purpose of the Study:
- To investigate the therapeutic potential of miR-146a-5p in osteoarthritis.
- To elucidate the underlying molecular mechanisms of miR-146a-5p in OA pathogenesis.
Main Methods:
- Human chondrocytes (C28/I2) were stimulated with SDF-1 to assess cell viability, necrosis, and autophagy markers (LC3-II, Beclin-1, autophagic flux).
- MiR-146a-5p mimics were transfected to evaluate its role in SDF-1/CXCR4-induced chondrocyte autophagy.
- A rabbit OA model induced by SDF-1 was used to assess the therapeutic effects of miR-146a-5p, including histological analysis and molecular marker assessment.
Main Results:
- SDF-1/CXCR4 signaling significantly promoted chondrocyte autophagy, inhibited proliferation, and induced necrosis.
- Overexpression of miR-146a-5p suppressed SDF-1/CXCR4-induced chondrocyte autophagy, CXCR4 expression, and necrosis.
- In vivo, miR-146a-5p treatment attenuated SDF-1-induced OA progression in rabbits, reducing cartilage damage and key molecular markers.
Conclusions:
- SDF-1/CXCR4 signaling exacerbates osteoarthritis by enhancing chondrocyte autophagy.
- MiR-146a-5p demonstrates therapeutic potential for osteoarthritis by inhibiting CXCR4 expression and suppressing SDF-1/CXCR4-mediated chondrocyte autophagy.
