Activin release from bone coupled to bone resorption in organ culture of neonatal mouse calvaria

Activin, a member of the transforming growth factor-beta (TGF-beta) superfa mily, is present in the bone matrix and assumed to be involved in the regul ation of bone formation. In the present study, me investigated whether the release of activin from bone is coupled with bone resorption, Neonatal mous e calvaria were cultured in the presence of various stimulators of bone res orption (parathyroid hormone [PTH], interleukin-1 beta, prostaglandin E-2) for up to 72 h, and the activin activity in the medium was measured using a specific bioassay for activin, Activin activity was accumulated in proport ion to the time- and dose-dependent increase in calcium release from bone i nto the medium (bone resorption), An inhibition of PTH-dependent bone resor ption by a bisphosphonate, disodium dichlormethane-1,1-bisphosphonic acid ( Cl2MBP), completely blocked release of activin activity from bone into the medium. In primary culture of calvarial cells, however, neither PTH nor Cl2 MBP affected activin production. These findings indicate that release of ac tivin activity from bone tissue is strongly coupled to bone resorption, Bec ause activin possesses osteogenic activities, activin released locally from bone might be involved in the regulation of bone formation in the physiolo gical process of bone remodeling, as has been suggested for TGF-beta. (C) 2 000 by Elsevier Science Inc, All rights reserved.