Bone continuously remodels in response to mechanical and physiological stre
sses, allowing vertebrates to renew bone as adults. Bone remodeling consist
s of the cycled synthesis and resorption of collagenous and noncollagenous
extracellular matrix proteins, and an imbalance in this process can lead to
disease states such as osteoporosis, or more rarely osteopetrosis. There i
s evidence that the extracellular matrix glycoprotein osteonectin or secret
ed protein acidic and rich in cysteine (BM-40) may be important in bone rem
odeling. Osteonectin is abundant in bone and is expressed in areas of activ
e remodeling outside the skeleton. In vitro studies indicate that osteonect
in can bind collagen and regulate angiogenesis, metalloproteinase expressio
n, cell proliferation, and cell-matrix interactions. In some osteopenic sta
tes, such as osteogenesis imperfecta and selected animal models for bone fr
agility, osteonectin expression is decreased. To determine the function of
osteonectin in bone, we used contact x-ray, histomorphometry and Northern b
lot analysis to characterize the skeletal phenotype of osteonectin-null mic
e. We found that osteonectin-null mice have decreased bone formation and de
creased osteoblast and osteoclast surface and number, leading to decreased
bone remodeling with a negative bone balance and causing profound osteopeni
a. These data indicate that osteonectin supports hone remodeling and the ma
intenance of bone mass in vertebrates.