Fibroblast Growth Factor 19 Disrupts Cartilage Development Via the FGFR4/β-catenin Axis

Hao Chen1, Yujia Cui1, Jiazhou Li1

  • 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Insights

Fibroblast growth factor 19 (FGF19) impairs cartilage development by inhibiting chondrocyte maturation and growth plate thickness. This occurs through the FGFR4/β-catenin pathway, affecting skeletal growth.

Area of Science:

  • Skeletal Biology
  • Endocrinology
  • Developmental Biology

Background:

  • Fibroblast growth factor 19 (FGF19) is implicated in skeletal metabolic disorders.
  • The specific role of FGF19 in cartilage development remains unclear.

Purpose of the Study:

  • To investigate the influence of FGF19 on cartilage development and chondrogenesis.
  • To elucidate the molecular mechanisms underlying FGF19's effects on growth plate chondrocytes.

Main Methods:

  • Utilized an ex vivo metatarsal organ model for neonatal cartilage.
  • Employed an adeno-associated virus (AAV)-FGF19 overexpression model in adolescent growth plates.
  • Assessed chondrocyte differentiation, maturation, and proliferation markers.

Main Results:

  • FGF19 impaired chondrocyte maturation in neonatal models and reduced growth plate thickness in adolescent models.
  • FGF19 decreased mesenchymal stem cell chondrogenic differentiation and chondrocyte maturation by downregulating Wnt/β-catenin signaling.
  • FGF19 signaling, via FGFR4 and β-klotho (KLB), activated Wnt antagonists (SFRP1, WIF1, DKK2), inhibiting chondrocyte proliferation and cartilage growth.

Conclusions:

  • FGF19 inhibits cartilage development and growth plate chondrogenesis through the FGFR4/β-catenin axis.
  • This study provides novel insights into the role of FGF19 in endochondral ossification and skeletal development.

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