Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3

Barbara D. Boyan, Zvi Schwartz, Shaun Park-Snyder, David D. Dean, Funmei Yang, Daniel Twardzik, Lynda F. Bonewald

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Resting zone and growth zone (GC) costochondral chondrocytes constitutively release latent, but not active, transforming growth factor-β (TGF-β) into the culture medium. When exogenous TGF-β is added to the culture medium, no autocrine effect is observed. However, when 1,25-(OH)2D3 is added, a dose-dependent inhibition of latent TGF-β release is found. Messenger RNA levels for TGF-β1 are unchanged by treatment with either 1,25- (OH)2D3 or TGF-β1. Since active growth factor was not observed in the conditioned medium, we tested the hypothesis that latent TGF-β could be activated in the matrix. GC matrix vesicles, extracellular organelles associated with matrix calcification, were able to activate latent TGF-β1 and TGF-β2 when preincubated with 1,25-(OH)2D3. In contrast, GC plasma membranes activated latent TGF-β, and addition of 1,25-(OH)2D3 inhibited this activation. The 1,25-(OH)2D3-dependent decrease in latent TGF-β in the medium, with no detectable change in mRNA level, and the inhibition of plasma membrane activation of latent TGF-β by 1,25-(OH)2D3 suggest that 1,25-(OH)2D3 may act through post-transcriptional and/or nongenomic mechanisms. The results also suggest that latent TGF-β is activated in the matrix and that 1,25-(OH)2D3 regulates this activation by a direct, nongenomic action on the matrix vesicle membrane.

Original languageEnglish (US)
Pages (from-to)28374-28381
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number45
StatePublished - Nov 11 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Boyan, B. D., Schwartz, Z., Park-Snyder, S., Dean, D. D., Yang, F., Twardzik, D., & Bonewald, L. F. (1994). Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3. Journal of Biological Chemistry, 269(45), 28374-28381.