Jichu yixue yu linchuang (Nov 2024)

Down-regulation of FGFR3 expression aggravates the damage of articular chondrocyte superficial zone cells in mice

  • GUAN Yunbo, LI Chao, XU Cheng, SUN Xiaofei, BAI Xuedong, HE Qing, WANG Zuqiang

DOI
https://doi.org/10.16352/j.issn.1001-6325.2024.11.1530
Journal volume & issue
Vol. 44, no. 11
pp. 1530 – 1537

Abstract

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Objective To investigate the effect of fibroblast growth factor receptor 3 (FGFR3) on articular cartilage superficial zone cells (SPZCs). Methods C57 mice were randomly divided into two groups: a sham operated group (sham group) and a group of surgically induced unstable medial meniscus model group (DMM group). The histological morphology of articular cartilage was microscopied by Safranin O/Fast Green-stained in 4 weeks and 8 weeks after surgery. Apoptosis and FGFR3 protein expression were detected by immunohistochemical staining microscopy. Primary SPZCs were separated and randomly divided into control group and Fgfr3 knockdown treatment group. The genes and protein expression related to chondrocyte extra cellular matrix synthesis, degradation and chondrocytehypertrophy were detected by RT-qPCR and Western blot. Results Compared with the sham group, the keen cartilage of mice in DMM group showed a pioneer damage of SPZCs after surgery; Immunohistochemistry results showed an increase in chondrocyte apoptosis and a decrease in expression of MMP-13 and FGFR3(P＜0.05). Primary SPZCs were transfected with small interfering RNA (siRNA) to knockdown Fgfr3; RT-qPCR results showed that the mRNA expression of genes related to the synthesis of cartilage extracellular matrix aggrecan and Col2 was reduced; And the mRNA expression of extracellular matrix degradation-related genes Mmp13 and Adamts5 was increased. The mRNA expression of chondrocyte hypertrophy-related genes Col10 and Mmp13 was increased. Western blot and RT-qPCR results were consistent and the expression l of MMP13 protein was significantly increased, while the expression of collagen Ⅱ and aggrecan protein was significantly decreased (P＜0.05). Conclusions Knockdown of Fgfr3 induces damage to primary SPZCs in mice resulting in early osteoarthritis (OA) development.

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