Growth factors and bone formation in osteoporosis: roles for fibroblast growth factor and transforming growth factor...

Osteoporosis is characterised by excess bone fragility resulting from bone loss and altered bone microarchitecture. Bone loss occurring during aging and after menopause in women is known to result from an imbalance between bone formation and resorption. Bone formation is dependent on the commitment of osteoprogenitor cells, the proliferation of pre-osteoblasts, their differentiation into mature osteoblasts synthesising bone matrix and the life-span of mature osteoblasts. Transforming Growth Factor beta (TGFbeta) and Fibroblast Growth Factors (FGFs) are important factors that promote osteoprogenitor cell proliferation and osteogenesis. Reduced expression of TGFbeta in bone was found in several animal models of osteopenia. In addition, both FGF and TGFbeta were found to exert anabolic effects on bone formation in intact animals and to reduce bone loss in experimental models of osteoporosis. Both genetic manipulation of FGF and TGFbeta or their receptors in mice and bone phenotype associated with FGF receptors and TGFbeta mutations or polymorphism suggest that TGFbeta and FGF signalling may contribute to the control of osteogenesis and bone mass in vivo. The determination of molecular mechanisms involved in the anabolic actions of FGF and TGFbeta in cells of the osteoblastic lineage may lead in the future to the development of new therapeutic strategies aimed at improving bone formation in osteoporotic patients.