Osteonectin-null mutation compromises osteoblast formation, maturation, and survival.
Osteonectin, also known as SPARC (secreted protein acidic and rich in cysteine) or BM-40, is one of the most abundant noncollagenous proteins in bone. Analysis of osteonectin-null mice revealed that osteonectin is necessary for the maintenance of bone mass and normal remodeling, as osteonectin-null mice have decreased osteoblast number and bone formation rate. Cultures of bone marrow stromal cells and osteoblasts from control and osteonectin-null mice were used to determine the cellular basis for the mutant phenotype. We found that marrow stroma from osteonectin-null mice contains fewer osteoblastic precursors than that of control mice, and the osteonectin-null mutation did not affect the proliferation rate of stromal cells or osteoblasts. Whereas osteonectin-null cells could adopt an osteoblastic phenotype, a smaller proportion of these cells expressed markers of a fully differentiated osteoblast. Mutant cells exhibited decreased formation of mineralized nodules, as well as diminished expression of osteocalcin mRNA and response to PTH. Furthermore, osteonectin-null cells showed an increased tendency to form adipocytes, with enhanced expression of the adipocytic markers adipsin and CCAAT/enhancer binding protein delta. Osteonectin-null cells were also more susceptible to environmental stresses. These data indicate that osteonectin is important for osteoblast formation, maturation, and survival.
Delany
Anne M
AM
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA. adelany@stfranciscare.org
Kalajzic
Ivo
I
Bradshaw
Amy D
AD
Sage
E Helene
EH
Canalis
Ernesto
E
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D012886:Skull / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology
D015676:Osteonectin