DOI: 10.1359/jbmr.1999.14.4.475. BMP-6 Is an Autocrine Stimulator of Chondrocyte Differentiation

BMP-6 Is an Autocrine Stimulator of Chondrocyte Differentiation

10.1359/jbmr.1999.14.4.475

Crossref journal-article

Oxford University Press (OUP)

Journal of Bone and Mineral Research (286)

Abstract

Abstract While parathyroid hormone-related protein (PTHrP) has been characterized as an important negative regulator of chondrocyte maturation in the growth plate, the autocrine or paracrine factors that stimulate chondrocyte maturation are not well characterized. Cephalic sternal chondrocytes were isolated from 13-day embryos, and the role of bone morphogenetic protein-6 (BMP-6) as a positive regulator of chondrocyte maturation was examined in monolayer cultures. Progressive maturation, which was accelerated in the presence of ascorbate, occurred in the cultures. During maturation, the cultures expressed high levels of BMP-6 mRNA which preceded the induction of type X collagen mRNA. Treatment of the cultures with PTHrP (10−7 M) at the time of plating completely abolished BMP-6 and type X collagen mRNA expression. Removal of PTHrP after 6 days was followed by the rapid (within 24 h) expression of BMP-6 and type X collagen mRNA, with BMP-6 again preceding type X collagen expression. The addition of exogenous BMP-6 (100 ng/ml) to the cultures accelerated the maturation process both in the presence and absence of ascorbate and resulted in the highest levels of type X collagen. When exogenous BMP-6 was added to PTHrP containing cultures, maturation occurred with the expression of high levels of type X collagen, despite the presence of PTHrP in the cultures. Furthermore, BMP-6 did not stimulate expression of its own mRNA in the PTHrP treated cultures, but it did stimulate the expression of Indian hedgehog (Ihh) mRNA. These latter findings suggest that while PTHrP directly inhibits BMP-6, it indirectly regulates Ihh expression through BMP-6. Other phenotypic changes associated with chondrocyte differentiation were also stimulated by BMP-6, including increased alkaline phosphatase activity and decreased proliferation. The results suggest that BMP-6 is an autocrine factor that initiates chondrocyte maturation and that PTHrP may prevent maturation by inhibiting the expression of BMP-6.

Bibliography

Grimsrud, C. D., Romano, P. R., Dâsouza, M., Puzas, J. E., Reynolds, P. R., Rosier, R. N., & Oâkeefe, R. J. (1999). BMP-6 Is an Autocrine Stimulator of Chondrocyte Differentiation. Journal of Bone and Mineral Research, 14(4), 475â482.

Authors 7

Christopher D. Grimsrud (first)
Paul R. Romano (additional)
Mary D'souza (additional)
J. Edward Puzas (additional)
Paul R. Reynolds (additional)
Randy N. Rosier (additional)
Regis J. O'keefe (additional)

References 35 Referenced 149

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{'key': '2024020713382059700_bib4', 'first-page': '131', 'article-title': 'Regulation of mineralization-competent matrix vesicle production in hypertrophic chondrocytes', 'volume': '22', 'author': 'Kirch', 'year': '1997', 'journal-title': 'Trans Orthop Res Soc'} / Trans Orthop Res Soc / Regulation of mineralization-competent matrix vesicle production in hypertrophic chondrocytes by Kirch (1997)
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Dates

Type	When
Created	19 years, 4 months ago (April 26, 2006, 9:11 p.m.)
Deposited	1 year, 5 months ago (March 13, 2024, 10:57 a.m.)
Indexed	8 months ago (Dec. 30, 2024, 1:13 p.m.)
Issued	26 years, 5 months ago (April 1, 1999)
Published	26 years, 5 months ago (April 1, 1999)
Published Online	15 years, 9 months ago (Dec. 2, 2009)
Published Print	26 years, 5 months ago (April 1, 1999)

Funders 0

None

BibTeX

@article{Grimsrud_1999, title={BMP-6 Is an Autocrine Stimulator of Chondrocyte Differentiation}, volume={14}, ISSN={1523-4681}, url={http://dx.doi.org/10.1359/jbmr.1999.14.4.475}, DOI={10.1359/jbmr.1999.14.4.475}, number={4}, journal={Journal of Bone and Mineral Research}, publisher={Oxford University Press (OUP)}, author={Grimsrud, Christopher D. and Romano, Paul R. and D’souza, Mary and Puzas, J. Edward and Reynolds, Paul R. and Rosier, Randy N. and O’keefe, Regis J.}, year={1999}, month=apr, pages={475–482} }

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