TGF-BETA-2 PREVENTS THE IMPAIRED CHONDROCYTE PROLIFERATION INDUCED BYUNLOADING IN GROWTH PLATES OF YOUNG-RATS

Growth plate width and cartilage organization are altered during skele tal unloading in growing rats. Immunohistochemical studies have identi fied TGF-beta in calcified cartilage, and TGF-beta is known to induce mitogenic effects on chondrocytes in vitro: On the other hand, IGF-1 w as shown to be expressed in the proximal tibial growth plate and to me diate GH-induced longitudinal bone growth in rats. We therefore invest igated the effect of recombinant human (rh) IGF-1 and rhTGF-beta 2 inf usion on the changes induced by unloading in the cellular organization of the growth plate in growing rats. Hindlimb unloading for 14 days i nduced a 13% reduction in growth cartilage height in the proximal tibi a. This effect was mostly related to a 17% and 14% decrease in the pro liferative zone height and chondrocyte number, respectively. In unload ed rats treated with a systemic infusion of rhTGF-beta 2 (2 mu g/kg/da y) the number of chondrocytes in the proliferative zone was not differ ent from those of normal loaded animals. In contrast, rhIGF-1 treatmen t at a 2mg/kg/day dose was not effective in counteracting the effects of unloading on growth plate height and chondrocyte number. These resu lts show that systemic administration of rhTGF-beta 2 prevents in larg e part the reduced growth of chondrocytes in the proliferative zone an d the reduced epiphyseal growth plate growth induced by unloading in r ats.