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Bone remodeling depends on the precise coordination of bone resorption and subsequent bone formation. Disturbances of this process are associated with skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in vitro and in vivo models that active TGF-[beta]1 released during bone resorption coordinates bone formation by inducing migration of bone marrow stromal cells, also known as bone mesenchymal stem cells, to the bone resorptive sites and that this process is mediated through a SMAD signaling pathway. Analyzing mice carrying a CED-derived mutant TGFB1 (encoding TGF-[beta]1), which show the typical progressive diaphyseal dysplasia seen in the human disease, we found high levels of active TGF-[beta]1 in the bone marrow. Treatment with a TGF-[beta] type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-[beta]1 functions to couple bone resorption and formation, modulation of TGF-[beta]1 activity could be an effective treatment for bone remodeling diseases., In the adult skeleton, bone is continuously being formed and resorbed, not only to maintain mineral homeostasis but also to cope with the microfractures that occur as a consequence of [...]

Limb growth depends on the proliferation of mesenchyme by stimulation of a specialized epithelium at the limb tip known as the apical ectodermal ridge (AER). Both the genes fibroblast growth factor-4 and bone morphogenetic protein-2 are expressed by mouse AER. These encode the secreted signalling molecules FGF-4 and BMP-2, respectively. It has been found that FGF-4 stimulates growth of mesenchyme in early mouse limb-buds and that BMP-2 inhibits this growth. This suggests limb growth depends on a mixture of stimulatory and inhibitory signals.

To maintain skeletal integrity and prevent fractures, degradation and rebuilding of bone must occur in synchrony. Transforming growth factor-?1 is now found to coordinate this restructuring process: the molecule is released during bone degradation and stimulates bone rebuilding (pages 757-765)., Although often depicted in the lay media and cartoons as a hunk of mineralized rock, bone in reality is a highly dynamic and specialized organ. As a connective tissue, bone [...]

Tissue engineering and gene therapy together can speed bone regeneration. Effective, rapid restoration of functional tissue as a therapeutic response to disease, injury, or aging is increasingly important.

Jan 8 A new drug combination that releases high levels of two types of stem cells--those that regenerate bone and repair blood vessels--from mouse bone marrow, might eventually lead to [...]