Hsiang-Hsi Hong and Nicole Pischon contributed equally to this work.
A role for lysyl oxidase regulation in the control of normal collagen deposition in differentiating osteoblast cultures†
Article first published online: 21 JAN 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 200, Issue 1, pages 53–62, July 2004
How to Cite
Hong, H.-H., Pischon, N., Santana, R. B., Palamakumbura, A. H., Chase, H. B., Gantz, D., Guo, Y., Uzel, M. I., Ma, D. and Trackman, P. C. (2004), A role for lysyl oxidase regulation in the control of normal collagen deposition in differentiating osteoblast cultures. J. Cell. Physiol., 200: 53–62. doi: 10.1002/jcp.10476
- Issue published online: 27 APR 2004
- Article first published online: 21 JAN 2004
- Manuscript Accepted: 8 OCT 2003
- Manuscript Received: 26 AUG 2003
- NIH. Grant Numbers: DE 12209, DE 14066
Differentiation of phenotypically normal osteoblast cultures leads to formation of a bone-like extracellular matrix in vitro. Maximum collagen synthesis occurs early in the life of these cultures, whereas insoluble collagen deposition occurs later and is accompanied by a diminished rate of collagen synthesis. The mechanisms that control collagen deposition seem likely to include regulation of extracellular collagen biosynthetic enzymes, but expression patterns of these enzymes in differentiating osteoblasts has received little attention. The present study determined the regulation of lysyl oxidase as a function of differentiation of phenotypically normal murine MC3T3-E1 cells at the level of RNA and protein expression and enzyme activity. In addition, the regulation of BMP-1/mTLD mRNA levels that encodes procollagen C-proteinases was assayed. The role of lysyl oxidase in controlling insoluble collagen accumulation was further investigated in inhibition studies utilizing β-aminopropionitrile, a specific inhibitor of lysyl oxidase enzyme activity. Results indicate that lysyl oxidase is regulated as a function of differentiation of MC3T3-E1 cells, and that the maximum increase in lysyl oxidase activity precedes the most efficient phase of insoluble collagen accumulation. By contrast BMP-1/mTLD is more constitutively expressed. Inhibition of lysyl oxidase in these cultures increases the accumulation of abnormal collagen fibrils, as determined by solubility studies and by electron microscopy. Taken together, these data support that regulation of lysyl oxidase activity plays a key role in the control of collagen deposition by osteoblast cultures. Copyright © 2004 Wiley-Liss, Inc.