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Journal article
Fibroblast Growth Factor 21 (FGF21) Inhibits Chondrocyte Function and Growth Hormone Action Directly at the Growth Plate
The Journal of biological chemistry, v 287(31), pp 26060-26067
27 Jul 2012
PMID: 22696219
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Evidence suggests that fibroblast growth factor 21 (FGF21) inhibits longitudinal bone growth.
Results: FGF21 antagonizes the growth hormone (GH) stimulatory effects on thymidine incorporation and collagen X expression in chondrocytes.
Conclusion: FGF21 inhibits bone growth by antagonizing GH effects on chondrocyte proliferation and differentiation.
Significance: Increased FGF21 during food restriction may contribute to growth failure by directly inhibiting chondrogenesis.
Fibroblast growth factor 21 (FGF21) modulates glucose and lipid metabolism during fasting. In addition, previous evidence indicates that increased expression of FGF21 during chronic food restriction is associated with reduced bone growth and growth hormone (GH) insensitivity. In light of the inhibitory effects on growth plate chondrogenesis mediated by other FGFs, we hypothesized that FGF21 causes growth inhibition by acting directly at the long bones' growth plate. We first demonstrated the expression of FGF21, FGFR1 and FGFR3 (two receptors known to be activated by FGF21) and β-klotho (a co-receptor required for the FGF21-mediated receptor binding and activation) in fetal and 3-week-old mouse growth plate chondrocytes. We then cultured mouse growth plate chondrocytes in the presence of graded concentrations of rhFGF21 (0.01–10 μg/ml). Higher concentrations of FGF21 (5 and 10 μg/ml) inhibited chondrocyte thymidine incorporation and collagen X mRNA expression. 10 ng/ml GH stimulated chondrocyte thymidine incorporation and collagen X mRNA expression, with both effects prevented by the addition in the culture medium of FGF21 in a concentration-dependent manner. In addition, FGF21 reduced GH binding in cultured chondrocytes. In cells transfected with FGFR1 siRNA or ERK 1 siRNA, the antagonistic effects of FGF21 on GH action were all prevented, supporting a specific effect of this growth factor in chondrocytes. Our findings suggest that increased expression of FGF21 during food restriction causes growth attenuation by antagonizing the GH stimulatory effects on chondrogenesis directly at the growth plate. In addition, high concentrations of FGF21 may directly suppress growth plate chondrocyte proliferation and differentiation.
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Details
- Title
- Fibroblast Growth Factor 21 (FGF21) Inhibits Chondrocyte Function and Growth Hormone Action Directly at the Growth Plate
- Creators
- Shufang Wu - St. Christopher's Hospital for ChildrenAmy Levenson - Drexel UniversityAlexei Kharitonenkov - Eli LillyFrancesco De Luca - St. Christopher's Hospital for Children
- Publication Details
- The Journal of biological chemistry, v 287(31), pp 26060-26067
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics; College of Medicine
- Web of Science ID
- WOS:000306916300033
- Scopus ID
- 2-s2.0-84864388774
- Other Identifier
- 991019168863404721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology