The Journal of Experimental Medicine
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Published online 5 February 2001.
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© The Rockefeller University Press, 0022-1007/2001/2/399/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 3, February 5, 2001 399-404

Brief Definitive Report

Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin

Muneaki Ishijimaa, Susan R. Rittlingb, Teruhito Yamashitaa, Kunikazu Tsujia, Hisashi Kurosawac, Akira Nifujia, David T. Denhardtb, and Masaki Nodaa

a Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
b Rutgers University, Piscataway, New Jersey 08854
c Juntendo University, Tokyo 113-8421, Japan
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10, Kanda-Surugadai 2-Chome, Chiyoda-Ku, Tokyo 101-0062, Japan.81-3-5280-806681-3-5280-8066

noda.mph{at}mri.tmd.ac.jp

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN–/– mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN–/– mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN–/– mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN–/– mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN–/– mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

Key Words: osteopontin • mechanical stress • osteoblasts • osteoclasts • tail suspension

© 2001 The Rockefeller University Press


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