Increased bone formation in osteocalcin-deficient mice

Duey, Patricia; Desbois, Christalle; Boyce, Brendan; Pinerot, Gerald; Story, Beryl; Dunstan, Colin; Smith, Erica; Bonadioll, Jeffrey; Goldstein, Steven; Gundberg, Caren; Bradley, Allan; Karsenty, Gerard

Affiliations

¹Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 45, Houston, Texas 77030, USA

²Department of Pathology, The University of Texas Health Science Center, San Antonio, Texas 78284, USA

³Department of Basic Science, Dental Branch University of Texas, Houston, Texas 77030, USA

⁴Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas 78284, USA

⁵Department of Orthopaedics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA

⁶Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, US

⁷Department of Orthopaedics, Yale School of Medicine, New Haven, Connecticut 06510, USA

⁸Howard Hughes Medical Institute and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA

Abstract

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.

Links

DOI: 10.1038/382448a0

PubMed: 8684484

WoS: A1996VA25100056

History

Received: 1996-03-19

Accepted: 281996-05-

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