Nature 382, 448 - 452 (01 August 1996); doi:10.1038/382448a0

Increased bone formation in osteocalcin-deficient mice

Patricia Ducy, Christelle Desbois, Brendan Boyce^*, Gerald Pinero^†, Beryl Story^*, Colin Dunstan^‡, Erica Smith^§, Jeffrey Bonadio, Steven Goldstein^§, Caren Gundberg^¶, Allan Bradley^£ & Gerard Karsenty

Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 45, Houston, Texas 77030, USA
Departments of ^* Pathology, and ^‡ Medicine, The University of Texas Health Science Center, San Antonio, Texas 78284, USA
^†Department of Basic Science, Dental Branch University of Texas, Houston, Texas 77030, USA
Departments of ^§Orthopaedics, and Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
^¶Department of Orthopaedics, Yale School of Medicine, New Haven, Connecticut 06510, USA
^£Howard Hughes Medical Institute and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA

VERTEBRATES constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity^1–3 have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein⁴, we have generated osteocalcin-deficient mice. These mice develop a phenotype marked by higher bone mass and bones of improved functional quality. Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formation.

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