Stimulation of bone formation in vivo by transforming growth factor-beta: remodeling of woven bone and lack of inhibition by indomethacin.
Local effects of transforming growth factor-beta (TGF beta) on bone have been investigated in growing mice. The influence of indomethacin on TGF beta effects was also examined. Five daily injections of TGF beta-1 or -2 were administered subcutaneously over the frontal and parietal bones of seven-week-old mice. In animals treated with TGF beta alone or TGF beta and indomethacin, then killed on day 19 (day 1 = day of first TGF beta injection), the combined frontal and parietal bones were heavier and the frontal bones were thicker than in controls. On day 4, multiple layers of differentiating osteoblasts were visible in the periosteum of calvariae from TGF beta-treated animals. On day 8, highly vascularised periosteal woven bone was seen in the calvariae of TGF beta-treated animals. On day 19 (14 days after the last injection) the woven bone had been partially remodeled into lamellar bone containing bone marrow, and was still actively being remodeled. The histological appearance of bones from animals treated concurrently with TGF beta and indomethacin was identical to that of animals treated with TGF beta alone, and there appeared to be no difference between TGF beta-1 and TGF beta-2. Thus TGF beta-stimulated bone formation in vivo is a long term effect that appears to be independent of prostaglandins. Osteoclast counts in sections of TGF beta-treated animals were not elevated on day 4, although at this stage effects on osteoblastic cells were already morphologically apparent. Osteoclast counts in TGF beta-treated bones were significantly increased over control values on days 8 and 19.(ABSTRACT TRUNCATED AT 250 WORDS)
Mackie
E J
EJ
Sandoz Ltd., Preclinical Research, Basel, Switzerland.
Trechsel
U
U
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D007213:Indomethacin