DOI: 10.1083/jcb.126.6.1595. Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.

Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.

10.1083/jcb.126.6.1595

Crossref journal-article

Rockefeller University Press

The Journal of cell biology (291)

Abstract

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta-related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation.

Bibliography

Gitelman, S. E., Kobrin, M. S., Ye, J. Q., Lopez, A. R., Lee, A., & Derynck, R. (1994). Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. The Journal of Cell Biology, 126(6), 1595â1609.

Authors 6

S E Gitelman (first)
M S Kobrin (additional)
J Q Ye (additional)
A R Lopez (additional)
A Lee (additional)
R Derynck (additional)

References 0 Referenced 121

None

Dates

Type	When
Created	21 years, 3 months ago (May 14, 2004, 8:22 p.m.)
Deposited	2 years, 1 month ago (July 21, 2023, 9:55 p.m.)
Indexed	11 months, 4 weeks ago (Sept. 7, 2024, 9:45 a.m.)
Issued	30 years, 11 months ago (Sept. 15, 1994)
Published	30 years, 11 months ago (Sept. 15, 1994)
Published Online	30 years, 11 months ago (Sept. 15, 1994)
Published Print	30 years, 11 months ago (Sept. 15, 1994)

Funders 0

None

BibTeX

@article{Gitelman_1994, title={Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.}, volume={126}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.126.6.1595}, DOI={10.1083/jcb.126.6.1595}, number={6}, journal={The Journal of cell biology}, publisher={Rockefeller University Press}, author={Gitelman, S E and Kobrin, M S and Ye, J Q and Lopez, A R and Lee, A and Derynck, R}, year={1994}, month=sep, pages={1595–1609} }

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