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 Bonewald

Research output: Contribution to journalArticle

88 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Transforming Growth Factors
Chondrocytes
Extracellular Matrix
Chemical activation
Cell membranes
Culture Media
Extracellular Vesicles
Cell Membrane
Messenger RNA
Conditioned Culture Medium
Organelles
Intercellular Signaling Peptides and Proteins
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3 . / Boyan, Barbara D.; Schwartz, Zvi; Park-Snyder, Shaun; Dean, David D.; Yang, Funmei; Twardzik, Daniel; Bonewald, Lynda.

In: Journal of Biological Chemistry, Vol. 269, No. 45, 11.11.1994, p. 28374-28381.

Research output: Contribution to journalArticle

Boyan, Barbara D. ; Schwartz, Zvi ; Park-Snyder, Shaun ; Dean, David D. ; Yang, Funmei ; Twardzik, Daniel ; Bonewald, Lynda. / Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3 In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 45. pp. 28374-28381.
@article{37f84410076248a7bde3ce7201ed940d,
title = "Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3",
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.",
author = "Boyan, {Barbara D.} and Zvi Schwartz and Shaun Park-Snyder and Dean, {David D.} and Funmei Yang and Daniel Twardzik and Lynda Bonewald",
year = "1994",
month = "11",
day = "11",
language = "English (US)",
volume = "269",
pages = "28374--28381",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "45",

}

TY - JOUR

T1 - Latent transforming growth factor-β is produced by chondrocytes and activated by extracellular matrix vesicles upon exposure to 1,25-(OH)2D3

AU - Boyan, Barbara D.

AU - Schwartz, Zvi

AU - Park-Snyder, Shaun

AU - Dean, David D.

AU - Yang, Funmei

AU - Twardzik, Daniel

AU - Bonewald, Lynda

PY - 1994/11/11

Y1 - 1994/11/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028030079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028030079&partnerID=8YFLogxK

M3 - Article

VL - 269

SP - 28374

EP - 28381

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 45

ER -