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Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
Aggrecan modulation of growth plate morphogenesis
Miriam S Domowicz1, Mauricio Cortes, Judith G Henry
1Departments of Pediatrics and Biochemistry and Molecular Biology, Committee on Developmental Biology, The University of Chicago, Chicago, IL 60637, USA.
Developmental Biology
|March 10, 2009
Summary
Aggrecan deficiency in chick embryos causes severe dwarfism by disrupting growth plate development. This leads to altered signaling pathways and premature maturation of chondrocytes, resulting in the nanomelic long bone disorder.
Area of Science:
- Skeletal biology and developmental disorders.
- Extracellular matrix and signaling pathways.
Background:
- Aggrecan is crucial for embryonic development, as evidenced by dwarfism and premature death in aggrecan-deficient embryos.
- Aggrecan's absence in nanomelic (nm) chick mutants leads to a severely compromised growth plate (GP) with altered cellular behavior.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the nanomelic long bone growth disorder caused by aggrecan deficiency.
- To elucidate the impact of aggrecan absence on signaling pathways within the developing chick growth plate.
Main Methods:
- Analysis of aggrecan-deficient (nm) chick embryos at various developmental stages (E6-E12).
- Assessment of chondroblast differentiation, proliferation, and cell death.
- Examination of key signaling pathway components including IHH, PTCH, FGFR3, ERK, COL10A1, and BMP signaling (P-SMAD1/5/8).
Main Results:
- While early chondroblast differentiation is normal, aggrecan deficiency alters IHH and FGF signaling pathways (PTCH, FGFR3, ERK) from the onset of GP formation.
- Premature expression of COL10A1 and altered IHH signaling accelerate chondrocyte hypertrophy.
- Disrupted BMP signaling (P-SMAD1/5/8) and delayed separation of growth plates contribute to the disorder.
Conclusions:
- Aggrecan is essential for normal growth plate formation and function.
- The absence of aggrecan disrupts multiple signaling pathways (IHH, FGF, BMP), leading to premature chondrocyte maturation and the nanomelic dwarfism phenotype.
- Early molecular alterations in the growth plate precede the severe skeletal abnormalities observed in aggrecan deficiency.
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