Downregulation of microRNA-574-3p expression in human lumbar disc degeneration and its improvement of degenerative changes in nucleus pulposus cells via targeting FGFR3.

OBJECTIVE

This study aimed to ascertain the involvement of microRNA-574-3p (miR-574-3p) in lumbar disc degeneration (LDD) pathogenesis, focusing on its interaction with fibroblast growth factor receptor 3 (FGFR3) and its potential as a therapeutic relevance.

METHODS

Degenerated and control nucleus pulposus (NP) tissues were collected from 72 patients. MiR-574-3p and FGFR3 expression were analyzed via qRT-PCR. In vitro, NP cells were treated with interleukin-1β (IL-1β) to model LDD, followed by the knockdown of miR-574-3p knockdown or modulation of FGFR3. Functional assays were conducted to assess proliferation, extracellular matrix markers, and target validation.

RESULTS

MiR-574-3p levels were markedly elevated in LDD tissues and exhibited a strong inverse correlation with FGFR3 expression (r = -0.6613, P < 0.001). In IL-1β-stimulated NP cells, miR-574-3p knockdown restored proliferation, elevated Collagen II/Aggrecan, and suppressed matrix metalloproteinase-3/13 (MMP-3/13) (P < 0.001). FGFR3 was verified as a direct target of miR-574-3p. Silencing FGFR3 counteracted the protective effects resulting from the knockdown of miR-574-3p.

CONCLUSIONS

MiR-574-3p serves as a critical regulator of NP cells homeostasis by suppressing FGFR3, offering clinical utility in LDD management as a biomarker and intervention target.