Systemic administration of recombinant transforming growth factor beta 2 (rTGF-beta 2) stimulates parameters of cancellous bone formation in juvenile and adult rats.
Transforming growth factor beta is a multifunctional protein with known actions on bone and bone cells. The ability of TGF-beta to stimulate osteogenic parameters in vitro and osteogenesis adjacent to injection sites in vivo is well established. The purpose of this study was to determine if systemic administration of recombinant TGF-beta 2 (rTGF-beta 2) could stimulate bone formation in rats of different ages. Juvenile (25-day-old) and adult (160-day-old) rats were treated daily for 5 days and 14 days, respectively, with rTGF-beta 2 given by subcutaneous injection. Bone formation was measured in cancellous bone of the lumbar vertebrae in juvenile rats and the femoral epiphysis in adult rats. Endochondral bone growth rates were measured in the distal femurs from both juvenile and adult rats using histomorphometric methods. Systemic administration of rTGF-beta 2 resulted in substantial increases in bone formation rates (both surface and volume referent) in both juvenile and adult rats. In the juvenile rats, rTGF-beta 2 increased the percent double labeled surface and the mineral appositional rate. In the adult rats, TGF-beta 2 treatment increased the double labeled surface and also endochondral (longitudinal) growth parameters without changing the number of osteoclasts or the number of osteoclast nuclei per cell. These results demonstrate that short-term systemic administration of rTGF-beta 2 substantially increases cancellous bone formation rate in rats.
Rosen
D
D
Celtrix Pharmaceuticals Inc., Santa Clara, CA 95054-1815.
Miller
S C
SC
DeLeon
E
E
Thompson
A Y
AY
Bentz
H
H
Mathews
M
M
Adams
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D005269:Femur / Q000187:drug effects / Q000254:growth & development*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta