INCREASED BONE FORMATION IN OSTEOCALCIN-DEFICIENT MICE

VERTEBRATES constantly remodel bone. The resorption of preexisting bon e by osteoclasts and the formation of new hone by osteoblasts is stric tly coordinated to maintain bone mass within defined limits. A fen mol ecular determinants of bone remodelling that affect osteoclast activit y(1-3) have been characterized, bot the molecular determinants of oste oblast activity are unknown. To investigate the role of osteocalcin, t he most abundant osteoblast-specific non-collagenous protein(4) we hav e 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 tha t the absence of osteocalcin leads to an increase in bone formation wi thout impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formatio n.