Altered hypertrophic chondrocyte kinetics in GDF-5 deficient murine tibial growth plates.
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.
Mikic
B
B
Picker Engineering Program, Smith College, 51 College Lane, Northampton, MA 01063, USA. bmikic@email.smith.edu
Clark
R T
RT
Battaglia
T C
TC
Gaschen
V
V
Hunziker
E B
EB
D000818:Animals; D001846:Bone Development; D019485:Bone Morphogenetic Proteins / Q000172:deficiency / Q000502:physiology*; D019902:Chondrocytes / Q000473:pathology*; D005260:Female; D055428:Growth Differentiation Factor 5; D006132:Growth Plate / Q000502:physiology*; D006984:Hypertrophy; D007700:Kinetics; D051379:Mice; D010012:Osteogenesis; D013977:Tibia / Q000166:cytology / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5