SYSTEMIC ADMINISTRATION OF TRANSFORMING GROWTH-FACTOR-BETA-2 PREVENTSTHE IMPAIRED BONE-FORMATION AND OSTEOPENIA INDUCED BY UNLOADING IN RATS

We investigated the effect of recombinant human transforming growth fa ctor beta 2 (rhTGF-beta 2) administration on trabecular bone loss indu ced by unloading in rats, Hind limb suspension for 14 d inhibited bone formation and induced osteopenia as shown by decreased bone volume, c alcium and protein contents in long bone metaphysis, Systemic infusion of rhTGF-beta 2 (2 mu g/kg per day) maintained normal bone formation rate, and prevented the decrease in bone volume, bone mineral content, trabecular thickness and number induced by unloading. In vitro analys is of tibial marrow stromal cells showed that rhTGF-beta 2 infusion in unloaded rats increased the proliferation of osteoblast precursor cel ls, but did not affect alkaline phosphatase activity or osteocalcin pr oduction, Northern blot analysis of RNA extracted from the femoral met aphysis showed that rhTGF-beta 2 infusion in unloaded rats increased s teady-state levels of type I collagen mRNA but not alkaline phosphatas e mRNA levels, rhTGF-beta 2 infusion at the dose used had no effect on metaphyseal bone volume and formation, osteoblast proliferation or co llagen expression in control rats, The results show that systemic admi nistration of rhTGF-beta 2 enhances osteoblast precursor cell prolifer ation and type I collagen expression by osteoblasts, and prevents the impaired bone formation and osteopenia induced by unloading.