Osteopenia and decreased bone formation in osteonectin-deficient mice.
Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists 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 is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates.
Delany
A M
AM
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Amling
M
M
Priemel
M
M
Howe
C
C
Baron
R
R
Canalis
E
E
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology*; D016723:Bone Remodeling; D002452:Cell Count; D017364:Collagenases / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000166:cytology; D015676:Osteonectin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging; D013977:Tibia / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D015676:Osteonectin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015675:Osteocalcin; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2