The effects of TGF-beta on bone.
The integrity of the skeleton is maintained by the continued cellular remodelling of bone that occurs throughout life and is characterized by an orderly sequence of events beginning with osteoclastic bone resorption followed by osteoblastic new bone formation to repair the localized defects made by osteoclasts. Bone resorption and formation are closely coupled by mechanisms which, until recently, have been poorly defined in both normal physiological and most pathological conditions, but are probably due to the generation during resorption of local 'coupling' factors. TGF-beta promises to be one of the key factors involved in coupling bone formation to previous bone resorption. This potent osteotropic polypeptide is abundant in the bone matrix, and is produced in response to factors that stimulate osteoclastic bone resorption. It is a very potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. TGF-beta has complex effects on bone resorption: it inhibits osteoclast formation and osteoclast activity. TGF-beta is released from bone in a biologically inert state that is due to the presence of at least two proteins which appear to regulate TGF-beta activity. Release of active TGF-beta from these latent complexes occurs during bone resorption and is mediated by osteoclasts. Knowledge of the mechanisms responsible for these activation processes may be vital to understanding the role of TGF-beta in bone remodelling.
Mundy
G R
GR
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
D000818:Animals; D001847:Bone Diseases / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D016212:Transforming Growth Factor beta