The role of bone morphogenetic protein-5 (BMP-5) in regulating chondrocytic
activity during endochondral ossification was examined in the mouse proxim
al tibial growth plate. Short ear mice homozygous for the SEA/Gn point muta
tion in the coding region for BMP-5 (King, J. A. et al, Dev Biol 166:112-12
2; 1994) and heterozygous long ear littermates were examined at 5 and 9 wee
ks of age (n = 9/group, four groups). Animals were injected with oxytetracy
cline to estimate the rate of growth and with bromodeoxyuridine to identify
proliferative chondrocytes. Age-related changes in chondrocytic stereologi
cal and kinetic parameters were compared by image analysis of 1-mu m-thick
growth plate sections. The number of proliferative chondrocytes did not var
y with age in either genotype, but proliferative phase duration increased s
ignificantly (similar to 67%) with age in the long ear mice, whereas no cha
nge was detected in the short ear mice. The number of hypertrophic chondroc
ytes increased significantly (similar to 27%) in the short ears, whereas th
is number decreased significantly (similar to 40%) in the long ears, There
was a small, but significant, increase in hypertrophic phase duration (simi
lar to 45%) in short ear mice, but no change was detected in the long ears.
These results indicate that BMP-5 deficiency prevents age-related decelera
tions in chondrocytic proliferation and initiation of hypertrophic differen
tiation, suggesting a role of BMP-5 in inhibiting these processes. (Bone 24
:211-216; 1999) (C) 1999 by Elsevier Science Inc. All rights reserved.