Altered osteoclast development and function in osteopontin deficient mice.
The role of osteopontin in bone resorption was elucidated by studies of mice with knock out of the osteopontin gene generated by a different approach compared to previous models. Thus, a targeting vector with the promoter region as well as exons 1, 2, and 3 of the osteopontin gene was replaced by a loxP-flanked Neo-TK cassette, and this cassette was eliminated through transient expression of Cre recombinase. The recombined ES cells were used to create mice lacking expression of the osteopontin gene. Tissues from these mice were subjected structural and molecular analyses including morphometry and proteomics. The bone of the null mice contained no osteopontin but showed no significant alterations with regard to other bone proteins. The bone volume was normal in young null animals but in the lower metaphysis, the volume and number of osteoclasts were increased. Notably, the volume and length of the osteoclast ruffled border was several folds lower, indicating a lower resorptive capacity. The null mice did not develop the bone loss characteristic for osteoporosis demonstrated in old wild-type female animals. This quantitative study demonstrates a bone phenotype in the osteopontin null mice of all ages. The data provides further evidence for a role of osteopontin in osteoclast activity.
Department of Experimental Medical Science, Lund University, BMC C12, SE-22184, Lund, Sweden.
Ahnders
A
Franzén
Kjell
K
Hultenby
Finn P
FP
Reinholt
Patrik
P
Onnerfjord
Dick
D
Heinegård
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D002460:Cell Line; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D058574:Integrin-Binding Sialoprotein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000502:physiology*; D053495:Osteopontin / Q000172:deficiency* / Q000502:physiology; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism
D016326:Extracellular Matrix Proteins; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D011509:Proteoglycans; D012795:Sialoglycoproteins; C113360:osteoadherin; D053495:Osteopontin