Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption

Osteopontin is one of the major noncollagenous bone matrix proteins produce d by osteoblasts and osteoclasts, bone cells that are uniquely responsible for the remodeling of mineralized tissues, Osteoclasts express the alpha v beta 3 integrin, which is one of the receptors for osteopontin, Recent knoc kout studies revealed that noncollagenous bone matrix proteins are function ally important in regulation of bone metabolism, However, the significance of the presence of osteopontin in in vivo has not been known. We report her e 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,mi ce, whereas the osteopontin-deficient mice exhibited only about 10% reducti on in trabecular bone volume after ovariectomy, Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice, i ndicating the specificity of the effect of osteopontin deficiency on bone m etabolism. We propose that osteopontin is essential for postmenopausal oste oporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.