EFFECT OF LOCAL INJECTION OF ACTIVIN-A ON BONE-FORMATION IN NEWBORN RATS

In order to examine the effect of activin A on the process of bone for mation, activin A was injected onto the periosteum of parietal bone in newborn rats, and the effect was compared with that of transforming g rowth factor (TGF)-beta. The daily periosteal injection of activin A i ncreased the thickness of both the periosteal and bone matrix layers i n a dose- and time-dependent manner. A maximal effect was obtained wit h 5.0 mu g/day activin A. The time course of the effect of activin A o n the periosteal thickness was similar to that of TGF-beta 1. However, the effect of TGF-beta 1 was much more pronounced and was mainly on f ibroblasts and inflammatory cells. The time course of the effect of ac tivin A on the thickness of bone matrix layer was different from that of TGF-beta 1. The effect of TGF-beta 1 reached maximum (1.8-fold) wit hin 3 days, whereas that of activin A did not develop until day 6 and reached maximum at the end of the 12-day injection period (1.4-fold). Histological examinations revealed that both TGF-beta 1 and activin A increased the number of alkaline phosphatase-positive osteoblastic cel ls. These results demonstrate that periosteal injection of activin A s timulates bone formation. In addition, although the possibility cannot be ruled out that the dramatic effect of TGF-beta 1 on the periosteal layer might have affected the delivery of TGF-beta 1 to the bone surf ace, these observations also suggest that the mode of action of activi n A may be different from that of TGF-beta 1. Because bone matrix cont ains abundant activin A, such an effect of activin A may have a signif icant role in the regulation of bone formation.