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

TLDR

Osteopontin, a major noncollagenous bone matrix protein expressed by osteoblasts and osteoclasts, binds the αvβ3 integrin on osteoclasts, and although knockout studies show noncollagenous proteins regulate bone metabolism, the in vivo role of osteopontin remained unclear. The authors propose that osteopontin is essential for postmenopausal osteoporosis and that counteracting its action may suppress the disease. Osteopontin‑deficient mice exhibit only ~10 % trabecular bone loss after ovariectomy compared to ~60 % in wild‑type, indicating that osteopontin deficiency protects bone while not affecting uterine weight loss.

Abstract

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 αvβ3 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.