Growth plate chondrocytes store latent transforming growth factor (TGF)- β1 in their matrix through latent TGF-β1 binding protein-1

H. A. Pedrozo, Z. Schwartz, R. Gomez, A. Ornoy, W. Xin-Sheng, S. L. Dallas, L. F. Bonewald, D. D. Dean, B. D. Boyan

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Osteoblasts produce a 100 kDa soluble form of latent transforming growth factor beta (TGF-β) as well as a 290 kDa form containing latent TGF-β binding protein-1 (LTBP1), which targets the latent complex to the matrix for storage. The nature of the soluble and stored forms of latent TGF-β in chondrocytes, however, is not known. In the present study, resting zone and growth zone chondrocytes from rat costochondral cartilage were cultured to fourth passage and then examined for the presence of mRNA coding for LTBP1 protein. In addition, the matrix and media were examined for LTBP1 protein and latent TGF-β. Northern blots, RT-PCR, and in situ hybridization showed that growth zone cells expressed higher levels of LTBP1 mRNA in vitro than resting zone cells. Immunohistochemical staining for LTBP1 revealed fine fibrillar structures around the cells and in the cell matrix. When the extracellular matrix of these cultures was digested with plasmin, LTBP1 was released, as determined by immunoprecipitation. Both active and latent TGF- β1 were found in these digests by TGF-β1 ELISA and Western blotting. Immunoprecipitation demonstrated that the cells also secrete LTBP1 which is not associated with latent TGF-β, in addition to LTBP1 that is associated with the 100 kDa latent TGF-β complex. These studies show for the first time that latent TGF-β is present in the matrix of costochondral chondrocytes and that LTBP1 is responsible for storage of this complex in the matrix. The data suggest that chondrocytes are able to regulate both the temporal and spatial activation of latent TGF-β, even at sites distant from the cell, in a relatively avascular environment.

Original languageEnglish (US)
Pages (from-to)343-354
Number of pages12
JournalJournal of cellular physiology
Volume177
Issue number2
DOIs
StatePublished - Nov 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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