EFFECTS OF RETINOL ON ACTIVATION OF LATENT TRANSFORMING GROWTH-FACTOR-BETA BY ISOLATED OSTEOCLASTS

The multifunctional cytokine, transforming growth factor-beta (TGF bet a), is found in many tissues in a latent or inactive form. The nature and composition of the latent complex can tissue type. The release of active TGF beta from its latent complex is a potentially important mec hanism for regulation of TGF beta activity. Wb have shown previously t hat Osteoclasts activate latent TGF beta produced by bone and that bon e cells produce a 100-kDa latent complex that lacks the latent TGF bet a-binding protein. Here we investigated the effects of retinol on oste oclast activation of various forms of latent TGF beta. Two sources of osteoclasts were used that provide either ma ture avian osteoclasts or avian osteoclast precursors. Whereas both cell populations activate l atent TGF beta, only mature osteoclasts respond to retinol with an inc rease in activation of latent TGF beta over basal levels. Activation c ould not be ascribed to pH changes in conditioned medium. Nonacid-diss ociable 100-kDa latent complex, which is also produced by bone cells, was added to mature osteoclasts and to osteoclast precursors, but no a ctivation was observed. Platelet latent TGF beta, which contains the 1 30-kDa latent TGF beta-binding protein, was activated,by both osteocla st populations. Conditioned medium from the precursor population activ ated. latent complex, whereas conditioned medium from mature cells did not. Activation of latent TGF beta by retinol-treated mature cells wa s not blocked by inhibitors of plasmin, nor was activation by conditio ned medium from precursor cells. These data, suggest that retinol-indu ced activation of latent TGF beta by osteoclasts is dependent on other stage of differentiation of these cells and the presence of other cel l types, and that unlike other cell systems, the plasmin-plasminogen a ctivator mechanism is not involved.