The control of chondrocyte differentiation during endochondral bone growth in vivo: changes in TGF-beta and the proto-oncogene c-myc.

The expression of transforming growth factor-beta and the c-myc proto-oncogene was studied in situ in the chondrocytes of the tibial growth plate of normal chicks and those with avian tibial dyschondroplasia in which the chondrocytes are developmentally arrested in the transitional phase between proliferation and differentiation. This results in an accumulation of unmineralised and avascular cartilage. Dyschondroplastic chicks showed reduced c-myc expression in the transitional chondrocytes but unaltered levels in the proliferating chondrocytes. Transforming growth factor-beta expression was reduced in the transitional chondrocytes of dyschondroplastic chicks. In areas where the lesion was being repaired there was evidence of increased expression of both c-myc protein and transforming growth factor-beta. Addition of 1,25-dihydroxyvitamin D to the diet, which is known to reduce the incidence of dyschondroplasia, resulted in an increase in c-myc production. These results suggest that both transforming growth factor-beta and the proto-oncogene c-myc may be important elements of the cascade of events that lead to chondrocyte differentiation, hypertrophy and mineralisation.