The multifunctional cytokine, transforming growth factor-β (TGFβ), is found in many tissues in a latent or inactive form. The nature and composition of the latent complex can vary depending on tissue type. The release of active TGFβ from its latent complex is a potentially important mechanism for regulation of TGFβ activity. We have shown previously that osteoclasts activate latent TGFβ produced by bone and that bone cells produce a 100-kDa latent complex that lacks the latent TGFβ-binding protein. Here we investigated the effects of retinol on osteoclast activation of various forms of latent TGFβ. Two sources of osteoclasts were used that provide either mature avian osteoclasts or avian osteoclast precursors. Whereas both cell populations activate latent TGFβ, only mature osteoclasts respond to retinol with an increase in activation of latent TGFβ over basal levels. Activation could not be ascribed to pH changes in conditioned medium. Nonacid-dissociable 100-kDa latent complex, which is also produced by bone cells, was added to mature osteoclasts and to osteoclast precursors, but no activation was observed. Platelets latent TGFβ, which contains the 130-kDa latent TGFβ-binding protein, was activated by both osteoclast populations. Conditioned medium from the precursor population activated latent complex whereas conditioned medium from mature cells did not. Activation of latent TGFβ by retinol-treated mature cells was not blocked by inhibitors of plasmin, nor was activation by conditioned medium from precursor cells. These data suggest that retinol-induced activation of latent TGFβ by osteoclasts is dependent on the stage of differentiation of these cells and the presence of other cell types, and that unlike other cell systems, the plasmin- plasminogen activator mechanism is not involved.
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