- Paper Report
- Open Access
BMP-2 induces osteoblast apoptosis mediated by PKC
- Tsutomu Takeuchi1
© Biomed Central Ltd 2002
- Received: 16 January 2002
- Accepted: 25 January 2002
- Published: 29 January 2002
Apoptosis of osteoblasts is a key to controlling osteoblast life span and bone formation, in addition to differentiation of progenitor cells. There are two types of regulators of osteoblast apoptosis: osteotropic hormones and local regulatory cytokines, such as tumor necrosis factor-a, interleukin-1 and -6, insulin-like growth factor-1, and fibroblast growth factor. Although it is well known that bone morphogenic proteins (BMPs) play a pivotal role in the commitment and differentiation of osteoblastic lineage, their role in apoptosis induction remains unknown.
BMP-2 promotes apoptosis in primary human calvariae and immortalized neonatal osteoblasts, while TGF-? inhibits apoptosis. BMP-2 increases the release of mitochondrial cytochrome c to the cytosol, the Bax/Bcl-2 ratio, and caspase-9, -3, -6, and -7 activity. When mutant Smad-1 is transfected in a dominant-negative fashion BMP-2-induced expression of osteoblast transcription factor Runx2 is downregulated, whereas the caspase activation and apoptosis is not affected. BMP-2 upregulates PKC activity and its inhibitor blocks osteoblasts-apoptosis induced by BMP-2, indicating that the proapoptotic effect of BMP-2 is PKC-dependent.
TUNEL-staining, in vitro enzyme activity measurements, western blot, in vitro transfection