Latent forms of transforming growth factor-? (TGF?) derived from bone cultures: identification of a naturally occurring 100-kDa complex with similarity to recombinant latent TGF?

Bonewald, L.F., Wakefield, L., Oreffo, R.O., Escobedo, A., Twardzik, D.R. and Mundy, G.R (1991) Latent forms of transforming growth factor-? (TGF?) derived from bone cultures: identification of a naturally occurring 100-kDa complex with similarity to recombinant latent TGF? Molecular endocrinology, 5 (6), 741-751. (PMID:1922093)

Abstract

Transforming growth factor-? (TGF?) is produced by most tissues, including bone, as a complex that is biologically inert. Release of TGF? homodimer from this latent complex is necessary for TGF? to exert effects on target cells. Thus, the nature of the latent complex and the mechanisms responsible for TGF? release are the key to understanding TGF? actions. We have found that murine calvarial bone cultures secrete multiple latent forms of TGF?. Using analytical chromatography and Western blot analysis, we have compared bone latent TGF? with the previously characterized latent complex present in platelets and with simian TGF? precursor, which is stably expressed in a latent form by Chinese hamster ovarian (CHO) cells. A major component of the bone material appears to be a latent complex of 100 kDa, consisting of mature TGF? (25-kDa homodimer). Like the recombinant TGF? precursor, it elutes from a Mono-Q fast pressure liquid chromatography anion exchange column at 0.2 M NaCl and shows a very similar banding pattern on Western blots. Thus, this bone complex closely resembles recombinant TGF? precursor expressed in a latent form by CHO cells and differs from the naturally occurring platelet complex, which has an additional 135-kDa binding protein that is bound through disulfide bonds to the precursor proregion. Western blot analysis also indicates that, like CHO cells, which express recombinant TGF? precursor, but unlike other cell types, the bone cultures secrete detectable amounts of uncleaved TGF? precursor. The bone calvarial culture is the first example of a naturally occurring system that expresses the 100-kDa latent TGF? complex.

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Contributors

Author: R.O. Oreffo

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