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Published on: December 3, 2016
Altered hypertrophic chondrocyte kinetics in GDF-5 deficient murine tibial growth plates
B Mikic1, R T Clark, T C Battaglia
1Picker Engineering Program, Smith College, 51 College Lane, Northampton, MA 01063, USA. bmikic@email.smith.edu
Abstract:
The growth/differentiation factors (GDFs) are a subgroup of the bone morphogenetic proteins best known for their role in joint formation and chondrogenesis. Mice deficient in one of these signaling proteins, GDF-5, exhibit numerous skeletal abnormalities, including shortened limb bones. The primary aim of this study was determine whether GDF-5 deficiency would alter the growth rate in growth plates from the long bones in mice and, if so, how this is achieved. Stereologic and cell kinetic parameters in proximal tibial growth plates from 5-week-old female GDF-5 -/- mice and control littermates were examined. GDF-5 deficiency resulted in a statistically significant reduction in growth rate (-14%, p=0.03). The effect of genotype on growth rate was associated with an altered hypertrophic phase duration, with hypertrophic cells from GDF-5 deficient mice exhibiting a significantly longer phase duration compared to control littermates (+25%, p=0.006). These data suggest that one way in which GDF-5 might modulate the rate of endochondral bone growth could be by affecting the duration of the hypertrophic phase in growth plate chondrocytes.
Insights
Growth/differentiation factor-5 (GDF-5) deficiency significantly reduces long bone growth rates in mice. This occurs due to a prolonged hypertrophic phase in growth plate chondrocytes, impacting endochondral ossification.
Area of Science:
- Skeletal biology
- Developmental biology
- Endocrinology
Background:
- Growth/differentiation factors (GDFs) are crucial bone morphogenetic proteins involved in skeletal development.
- GDF-5 plays a key role in joint formation and chondrogenesis.
- GDF-5 deficient mice display skeletal abnormalities, including shortened long bones.
Purpose of the Study:
- To investigate the impact of GDF-5 deficiency on long bone growth plate dynamics.
- To determine the cellular mechanisms underlying growth alterations in GDF-5 deficient mice.
Main Methods:
- Stereologic and cell kinetic analyses were performed on proximal tibial growth plates.
- Comparison between 5-week-old female GDF-5 knockout mice and wild-type littermates.
Main Results:
- GDF-5 deficiency led to a significant 14% reduction in growth rate (p=0.03).
- The hypertrophic zone chondrocyte phase duration was significantly extended by 25% (p=0.006) in GDF-5 deficient mice.
- These changes were associated with altered endochondral bone growth.
Conclusions:
- GDF-5 deficiency impairs long bone longitudinal growth.
- Modulation of the hypertrophic phase duration in growth plate chondrocytes is a key mechanism by which GDF-5 influences endochondral ossification.
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