Abstract
Growth plate width and cartilage organization are altered during skeletal unloading in growing rats. Immunohistochemical studies have identified TGF-β in calcified cartilage, and TGF-β is known to induce mitogenic effects on chondrocytes in vitro. On the other hand, IGF-1 was shown to be expressed in the proximal tibial growth plate and to mediate GH-induced longitudinal bone growth in rats. We therefore investigated the effect of recombinant human (rh) IGF-1 and rhTGF-β2 infusion on the changes induced by unloading in the cellular organization of the growth plate in growing rats. Hindlimb unloading for 14 days induced a 13% reduction in growth cartilage height in the proximal tibia. This effect was mostly related to a 17% and 14% decrease in the proliferative zone height and chondrocyte number, respectively. In unloaded rats treated with a systemic infusion of rhTGF-β2 (2μg/kg/day) the number of chondrocytes in the proliferative zone was not different from those of normal loaded animals. In contrast, rhIGF-1 treatment at a 2mg/kg/day dose was not effective in counteracting the effects of unloading on growth plate height and chondrocyte number. These results show that systemic administration of rhTGF-β2 prevents in large part the reduced growth of chondrocytes in the proliferative zone and the reduced epiphyseal growth plate growth induced by unloading in rats.
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