Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption.
Osteopontin is one of the major noncollagenous bone matrix proteins produced by osteoblasts and osteoclasts, bone cells that are uniquely responsible for the remodeling of mineralized tissues. Osteoclasts express the alphavbeta3 integrin, which is one of the receptors for osteopontin. Recent knockout studies revealed that noncollagenous bone matrix proteins are functionally important in regulation of bone metabolism. However, the significance of the presence of osteopontin in in vivo has not been known. We report here that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice. Microcomputed tomography analysis indicated about 60% reduction in bone volume by ovariectomy in wild-type mice, whereas the osteopontin-deficient mice exhibited only about 10% reduction in trabecular bone volume after ovariectomy. Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice, indicating the specificity of the effect of osteopontin deficiency on bone metabolism. We propose that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10 Kanda-Surugadai 2-Chome, Chiyoda-Ku, Tokyo, Japan.
H
H
Yoshitake
S R
SR
Rittling
D T
DT
Denhardt
M
M
Noda
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053495:Osteopontin; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology*; D010052:Ovariectomy; D010750:Phosphoproteins / Q000172:deficiency / Q000502:physiology; D012795:Sialoglycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D014057:Tomography, X-Ray Computed
D010750:Phosphoproteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin