Osteopenia and decreased bone formation in osteonectin-deficient mice

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.