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A Rat Tibial Growth Plate Injury Model to Characterize Repair Mechanisms and Evaluate Growth Plate Regeneration Strategies
Published on: July 4, 2017
Fibroblast growth factor expression in the postnatal growth plate
Jacob E Lazarus1, Anita Hegde, Anenisia C Andrade
1Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Bone
|December 16, 2006
Summary
Fibroblast growth factor (FGF) signaling regulates postnatal bone growth. This study quantifies FGFs and FGF receptors (FGFRs) in the growth plate, revealing spatial and temporal expression patterns crucial for skeletal development.
Area of Science:
- Skeletal Biology
- Endocrinology
- Molecular Biology
Background:
- Fibroblast growth factor (FGF) signaling is vital for endochondral bone formation.
- Mutations in FGF signaling pathways cause skeletal dysplasias like achondroplasia.
- Previous research primarily focused on embryonic chondrogenesis, leaving postnatal growth plate roles less understood.
Purpose of the Study:
- To investigate the role and regulation of FGF signaling in the postnatal growth plate.
- To quantify the expression of all known FGFs and major FGF receptor (FGFR) isoforms.
- To analyze the spatial and temporal expression patterns of FGFs and FGFRs within the growth plate.
Main Methods:
- Microdissection of rat proximal tibial growth plates and surrounding tissues.
- Quantitative analysis of specific FGF and FGFR mRNAs using real-time RT-PCR.
- Screening for expression of all known FGFs and major FGFR isoforms to ensure unbiased assessment.
Main Results:
- Identified expression of FGFs (1, 2, 6, 7, 9, 18, 21, 22) in the perichondrium and growth plate.
- Detected FGFRs 1, 2, 3 (primarily c-isoforms), and 4, along with FGFRL1, within the growth plate.
- Revealed distinct spatial expression patterns for FGFRs, with FGFR1 and 3 upregulated in later differentiation stages (hypertrophic zone) and FGFR2 and 4 in earlier stages (resting/proliferative zones).
- Observed temporal changes in FGFR2 and 4 expression, decreasing with age and reduced growth velocity, alongside upregulation of perichondrial FGFs.
- Discovered previously unknown FGF and FGFR expression in the postnatal growth plate and detailed their complex spatial and temporal regulation.
Conclusions:
- FGF and FGFR expression is spatially and temporally regulated within the postnatal growth plate.
- Differential expression of FGFRs suggests distinct roles in chondrocyte differentiation.
- Age-related changes in FGF/FGFR expression may contribute to growth plate senescence and final adult skeleton size.
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