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Thyroid hormone activates fibroblast growth factor receptor-1 in bone
David A Stevens1, Clare B Harvey, Anthea J Scott
1Molecular Endocrinology Group, Medical Research Council Clinical Sciences Centre, Clinical Research Building, 5th Floor, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Molecular Endocrinology (Baltimore, Md.)
|June 14, 2003
Summary
Thyroid hormone (T3) regulates bone development by upregulating fibroblast growth factor receptor-1 (FGFR1) in osteoblasts. This FGFR1 signaling pathway is crucial for bone health and thyroid disease-related skeletal disorders.
Area of Science:
- Endocrinology
- Bone Biology
- Molecular Signaling
Background:
- Thyroid hormone (T3) and its receptor alpha (TRalpha) are vital for bone development.
- Hyperthyroidism in adults elevates osteoporotic fracture risk.
- Thyroid hormone's role in bone remodeling and FGFR1 signaling is not fully understood.
Purpose of the Study:
- To investigate the role of fibroblast growth factor receptor-1 (FGFR1) as a T3-target gene in osteoblasts.
- To elucidate the mechanism by which T3 influences FGF2-mediated signaling in bone cells.
- To determine the in vivo relevance of FGFR1 in T3-dependent bone development.
Main Methods:
- Subtraction hybridization to identify T3-target genes in osteoblasts.
- Quantitative analysis of FGFR1 mRNA and protein expression following T3 treatment.
- Western blotting to assess MAPK and FRS2 phosphorylation.
- Pharmacological inhibition of FGFR1 signaling.
- In situ hybridization in TRalpha-knockout mice.
Main Results:
- FGFR1 was identified as a T3-target gene, with T3 significantly inducing FGFR1 mRNA and protein in osteoblasts.
- T3 pretreatment enhanced the magnitude and rapidity of FGF2-stimulated MAPK signaling and FGFR1 autophosphorylation.
- These T3-mediated effects on FGF signaling were dependent on TRalpha and abolished by FGFR inhibitors.
- TRalpha-knockout mice exhibited reduced FGFR1 expression and impaired responses to T3 and FGF2.
Conclusions:
- FGFR1 signaling is implicated as a key mediator of T3's effects on bone development.
- Dysregulation of FGFR1 signaling may contribute to skeletal pathologies associated with thyroid disease.
- Targeting FGFR1 may offer therapeutic potential for bone disorders linked to thyroid dysfunction.
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