THE BCL-2 KNOCKOUT MOUSE EXHIBITS MARKED CHANGES IN OSTEOBLAST PHENOTYPE AND COLLAGEN DEPOSITION IN BONE AS WELL AS A MILD GROWTH-PLATE PHENOTYPE

Histological examination of long bones from 1-day-old bcl-2 knockout a nd age-matched control mice revealed no obvious differences in length of bone, growth plate architecture or stage of endochondral ossificati on. In 35-day-old bcl-2 knockout mice that are growth retarded or 'dwa rfed', the proliferative zone of the growth plate appeared slightly th inner and the secondary centres of ossification less well developed th an their age-matched wild-type controls. The most marked histological effects of bcl-2 ablation were on osteoblasts and bone. 35-day-old kno ckout mouse bones exhibited far greater numbers of osteoblasts than co ntrols and the osteoblasts had a cuboidal phenotype in comparison with the normal flattened cell appearance. In addition, the collagen depos ited by the osteoblasts in the bcl-2 knockout mouse bone was disorgani zed in comparison with control tissue and had a pseudo-woven appearanc e. The results suggest an important role for Bcl-2 in controlling oste oblast phenotype and bone deposition in vivo.