Effects of retinol on activation of latent transforming growth factor-? by isolated osteoclasts

Bonewald, L.F., Oreffo, R.O., Lee, C.H., Park-Snyder, S., Twardzik, D. and Mundy, G.R. (1997) Effects of retinol on activation of latent transforming growth factor-? by isolated osteoclasts. Endocrinology, 138 (2), 657-666. (PMID:9003000)

Abstract

The multifunctional cytokine, transforming growth factor-beta (TGF?), 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 TGF? from its latent complex is a potentially important mechanism for regulation of TGF? activity. We have shown previously that osteoclasts activate latent TGF? produced by bone and that bone cells produce a 100-kDa latent complex that lacks the latent TGF?-binding protein. Here we investigated the effects of retinol on osteoclast activation of various forms of latent TGF?. Two sources of osteoclasts were used that provide either mature avian osteoclasts or avian osteoclast precursors. Whereas both cell populations activate latent TGF beta, only mature osteoclasts respond to retinol with an increase in activation of latent TGF? 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. Platelet latent TGF?, which contains the 130-kDa latent TGF?-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 TGF? 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 TGF? 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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Contributors

Author: R.O. Oreffo

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