DOI: 10.1083/jcb.145.4.783. Parathyroid Hormone–related Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor β (TGF-β) on Endochondral Bone Formation

Parathyroid Hormone–related Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor β (TGF-β) on Endochondral Bone Formation

10.1083/jcb.145.4.783

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Previously, we showed that expression of a dominant-negative form of the transforming growth factor β (TGF-β) type II receptor in skeletal tissue resulted in increased hypertrophic differentiation in growth plate and articular chondrocytes, suggesting a role for TGF-β in limiting terminal differentiation in vivo. Parathyroid hormone–related peptide (PTHrP) has also been demonstrated to regulate chondrocyte differentiation in vivo. Mice with targeted deletion of the PTHrP gene demonstrate increased endochondral bone formation, and misexpression of PTHrP in cartilage results in delayed bone formation due to slowed conversion of proliferative chondrocytes into hypertrophic chondrocytes. Since the development of skeletal elements requires the coordination of signals from several sources, this report tests the hypothesis that TGF-β and PTHrP act in a common signal cascade to regulate endochondral bone formation. Mouse embryonic metatarsal bone rudiments grown in organ culture were used to demonstrate that TGF-β inhibits several stages of endochondral bone formation, including chondrocyte proliferation, hypertrophic differentiation, and matrix mineralization. Treatment with TGF-β1 also stimulated the expression of PTHrP mRNA. PTHrP added to cultures inhibited hypertrophic differentiation and matrix mineralization but did not affect cell proliferation. Furthermore, terminal differentiation was not inhibited by TGF-β in metatarsal rudiments from PTHrP-null embryos; however, growth and matrix mineralization were still inhibited. The data support the model that TGF-β acts upstream of PTHrP to regulate the rate of hypertrophic differentiation and suggest that TGF-β has both PTHrP-dependent and PTHrP-independent effects on endochondral bone formation.

Bibliography

Serra, R., Karaplis, A., & Sohn, P. (1999). Parathyroid Hormoneârelated Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor Î² (TGF-Î²) on Endochondral Bone Formation. The Journal of Cell Biology, 145(4), 783â794.

Authors 3

Rosa Serra (first)
Andrew Karaplis (additional)
Philip Sohn (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 9:26 p.m.)
Indexed	11 months, 4 weeks ago (Sept. 4, 2024, 7:50 p.m.)
Issued	26 years, 3 months ago (May 17, 1999)
Published	26 years, 3 months ago (May 17, 1999)
Published Online	26 years, 3 months ago (May 17, 1999)
Published Print	26 years, 3 months ago (May 17, 1999)

Funders 0

None

BibTeX

@article{Serra_1999, title={Parathyroid Hormone–related Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor β (TGF-β) on Endochondral Bone Formation}, volume={145}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.145.4.783}, DOI={10.1083/jcb.145.4.783}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Serra, Rosa and Karaplis, Andrew and Sohn, Philip}, year={1999}, month=may, pages={783–794} }

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