BMP-5 deficiency alters chondrocytic activity in the mouse proximal tibial growth plate

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The role of bone morphogenetic protein-5 (BMP-5) in regulating chondrocytic activity during endochondral ossification was examined in the mouse proximal tibial growth plate. Short ear mice homozygous for the SEA/Gn point mutation in the coding region for BMP-5 (King, J. A. et al. Dev Biol 166:112–122; 1994) and heterozygous long ear littermates were examined at 5 and 9 weeks of age (n = 9/group, four groups). Animals were injected with oxytetracycline to estimate the rate of growth and with bromodeoxyuridine to identify proliferative chondrocytes. Age-related changes in chondrocytic stereological and kinetic parameters were compared by image analysis of 1-μm-thick growth plate sections. The number of proliferative chondrocytes did not vary with age in either genotype, but proliferative phase duration increased significantly (∼67%) with age in the long ear mice, whereas no change was detected in the short ear mice. The number of hypertrophic chondrocytes increased significantly (∼27%) in the short ears, whereas this number decreased significantly (∼40%) in the long ears. There was a small, but significant, increase in hypertrophic phase duration (∼45%) in short ear mice, but no change was detected in the long ears. These results indicate that BMP-5 deficiency prevents age-related decelerations in chondrocytic proliferation and initiation of hypertrophic differentiation, suggesting a role of BMP-5 in inhibiting these processes.