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Chondrocyte FGFR3 Regulates Bone Mass by Inhibiting Osteogenesis
Xuan Wen1, Xiaogang Li1,2, Yubin Tang1,3
1From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
The Journal of Biological Chemistry
|October 13, 2016
Summary
Removing Fibroblast Growth Factor Receptor 3 (FGFR3) from chondrocytes led to increased bone mass and enhanced bone formation and remodeling. This suggests FGFR3 in chondrocytes negatively regulates bone development.
Area of Science:
- Skeletal Biology
- Endocrinology
- Cell Biology
Background:
- Chondrogenesis plays a crucial role in bone formation.
- Fibroblast Growth Factor Receptor 3 (FGFR3), highly expressed in chondrocytes, is known to negatively regulate bone growth.
Purpose of the Study:
- To investigate the role of chondrocyte FGFR3 in regulating osteogenesis, postnatal bone formation, and bone remodeling.
Main Methods:
- Generation of mice with conditional knock-out of Fgfr3 in chondrocytes (mutant (MUT) mice).
- Analysis of bone mass, growth plate length, and histological examination of bone tissue.
- Chondrocyte-osteoblast co-culture assays to assess osteoblast differentiation and gene expression.
Main Results:
- MUT mice exhibited bone overgrowth with lengthened growth plates and significantly increased bone mass.
- Deletion of Fgfr3 in chondrocytes markedly enhanced osteoblast number and bone formation.
- FGFR3 deficiency in chondrocytes promoted osteoblast differentiation and mineralization, influencing key signaling pathways (e.g., Ihh, Bmp2, Bmp4, Bmp7, Wnt4, Tgf-β1, Nog).
- Osteoclastogenesis was impaired in MUT mice, potentially due to altered Rankl/Opg ratios.
Conclusions:
- Chondrocyte FGFR3 acts as a negative regulator of bone formation and remodeling.
- FGFR3 influences osteogenesis and osteoclastogenesis through paracrine mechanisms involving chondrocytes.
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