Mundy G R
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
Ciba Found Symp. 1991;157:137-43; discussion 143-51.
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.
骨骼的完整性通过一生中持续的骨细胞重塑得以维持，其特征是一系列有序的事件，始于破骨细胞的骨吸收，随后是成骨细胞形成新骨以修复破骨细胞造成的局部缺损。骨吸收和形成通过一些机制紧密耦合，直到最近，在正常生理和大多数病理情况下，这些机制都还没有得到很好的定义，但可能是由于在吸收过程中产生了局部“耦合”因子。转化生长因子-β（TGF-β）有望成为将骨形成与先前的骨吸收耦合起来的关键因子之一。这种强效的促骨生长多肽在骨基质中含量丰富，并在刺激破骨细胞骨吸收的因子作用下产生。它是成骨细胞骨形成的非常有效的刺激物，可导致定向成骨细胞的趋化性、增殖和分化。TGF-β对骨吸收有复杂的影响：它抑制破骨细胞的形成和破骨细胞的活性。TGF-β以生物学惰性状态从骨中释放出来，这是由于至少存在两种似乎调节TGF-β活性的蛋白质。活性TGF-β从这些潜伏复合物中的释放发生在骨吸收过程中，并由破骨细胞介导。了解这些激活过程的机制对于理解TGF-β在骨重塑中的作用可能至关重要。
