This work was presented in abstract form at the November 1998 meeting of the American College of Rheumatology, San Diego, California, U.S.A.
Matrix Vesicle Plasma Cell Membrane Glycoprotein-1 Regulates Mineralization by Murine Osteoblastic MC3T3 Cells†
Version of Record online: 1 JUN 1999
Copyright © 1999 ASBMR
Journal of Bone and Mineral Research
Volume 14, Issue 6, pages 883–892, June 1999
How to Cite
Johnson, K., Moffa, A., Chen, Y., Pritzker, K., Goding, J. and Terkeltaub, R. (1999), Matrix Vesicle Plasma Cell Membrane Glycoprotein-1 Regulates Mineralization by Murine Osteoblastic MC3T3 Cells. J Bone Miner Res, 14: 883–892. doi: 10.1359/jbmr.1922.214.171.1243
- Issue online: 2 DEC 2009
- Version of Record online: 1 JUN 1999
- Manuscript Accepted: 18 JAN 1999
- Manuscript Revised: 18 DEC 1998
- Manuscript Received: 16 OCT 1998
A naturally occurring nonsense truncation mutation of the inorganic pyrophosphate (PPi)-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) PC-1 is associated with spinal and periarticular ligament hyperostosis and cartilage calcification in “tiptoe walking” (ttw) mice. Thus, we tested the hypothesis that PC-1 acts directly in the extracellular matrix to restrain mineralization. Cultured osteoblastic MC3T3 cells expressed PC-1 mRNA and produced hydroxyapatite deposits at 12–14 days. NTPPPH activity increased steadily over 14 days. Transforming growth factor-β and 1,25-dihydroxyvitamin D3 increased PC-1 and NTPPPH in matrix vesicles (MVs). Because PC-1/NTPPPH was regulated in mineralizing MC3T3 cells, we stably transfected or infected cells with recombinant adenovirus, in order to express 2- to 6-fold more PC-1. PC-1/NTPPPH and PPi content increased severalfold in MVs derived from cells transfected with PC-1. Furthermore, MC3T3 cells transfected with PC-1 deposited ∼80–90% less hydroxyapatite (by weight) than cells transfected with empty plasmid or enzymatically inactive PC-1. ATP-dependent45Ca precipitation by MVs from cells overexpressing active PC-1 was comparably diminished. Thus, regulation of PC-1 controls the PPi content and function of osteoblast-derived MVs and matrix hydroxyapatite deposition. PC-1 may provide a novel therapeutic target in certain disorders of bone mineralization.