FIG. 9.

Proposed mechanism by which inhibition of microtubule assembly regulates Gli2 and BMP-2 in osteoblasts. Microtubule inhibitors cause inhibition of microtubule assembly and disassociation of the microtubule-Gli complex in osteoblastic cells. This in turn impairs the E3 ligase β-TrCP-dependent proteolytic processing of Gli2 in the proteasome, resulting in accumulation of Gli2 within cells. In turn, increased concentrations of Gli2 lead to enhanced transactivation of the BMP-2 gene and consequently increased osteoblast differentiation and new bone formation.