Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.
TGF-beta 1 is a polypeptide that is abundant in bone matrix, is produced by bone cells, and modulates proliferation and differentiated functions of osteoblastic cells in vitro. TGF-beta 2 is a closely related polypeptide that was originally isolated from bone matrix. TGF-beta 1 has been shown previously to stimulate prostaglandin production in cultures of neonatal mouse calvariae, which causes these bones to resorb. We found similar effects with TGF-beta 2. In comparison, TGF-beta 1 and TGF-beta 2 failed to stimulate bone resorption in fetal rat long bone cultures during a 3-d incubation period in concentrations up to 50-100 times greater than those capable of inducing bone resorption in calvariae. Incubation with TGF-beta 1 for a further 3 d decreased bone resorption up to 30%. Moreover, bone resorption induced by the bone-resorbing agents IL 1 and 1,25-dihydroxyvitamin D3 was partially or completely inhibited by TGF-beta 1 and TGF-beta 2 during the second half of the 6-d incubation period. Inhibition of DNA synthesis with hydroxyurea inhibited bone resorption in long bones in a similar pattern to that seen with TGF-beta 1. The inhibitory effects of TGF-beta 1 and TGF-beta 2 on bone resorption in long bone cultures may therefore be due to inhibition of osteoclast precursor proliferation.
Pfeilschifter
J
J
Department of Medicine/Endocrinology, University of Texas Health Science Center, San Antonio 78284.
Seyedin
S M
SM
Mundy
G R
GR
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011884:Radius / Q000166:cytology / Q000502:physiology*; D051381:Rats; D012886:Skull; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D013997:Time Factors; D015291:Transforming Growth Factors; D014457:Ulna / Q000166:cytology / Q000502:physiology*
D006131:Growth Inhibitors; D010455:Peptides; D015291:Transforming Growth Factors