Bone mass protective potential mediated by bovine milk basic protein requires normal calcium homeostasis in mice
Bone mass protective potential mediated by bovine milk basic protein requires normal calcium homeostasis in mice
复制标题
牛乳碱性蛋白介导的骨量保护潜力需要小鼠正常的钙稳态
DOI：
10.1016/j.nut.2021.111409
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发表时间：
2021
期刊：
影响因子：
4.4
通讯作者：
and Masuyama R.
中科院分区：
文献类型：
--
作者：
Ono-Ohmachi A;Ishida Y;Morita Y;Kato K;Yamanaka H;and Masuyama R.
牛奶对钙平衡受损引起的骨质流失具有保护作用。虽然一些元素的影响已经被证实，但牛奶碱性蛋白（MBP）在骨矿物质代谢中的作用仍然不清楚。此外，必须评估矿物质营养充足对建立MBP效果的重要性。首先，为了评估MBP活性所需的生理条件，我们检测了由于缺乏肠道维生素D信号而导致钙吸收不足的小鼠的骨骼和矿物质表型。其次，为了确定维生素D信号是否会影响MBP对骨吸收的作用，我们使用骨髓细胞评估了体外破骨细胞发生。结果在系统性维生素D受体（Vdr）失活的小鼠中，膳食补充MBP不能使高钙血症和甲状旁腺功能亢进正常化，也不能挽救骨矿化损伤。相反，当Vdr失活仅限于肠道时，钙和骨稳态对MBP补充有反应。补充MBP也改善了肠道特异性Vdr基因敲除小鼠的甲状旁腺功能亢进，同时降低了骨吸收，以响应血清抗酒石酸酸性磷酸酶5b的水平。这些结果与抗酒石酸酸性磷酸酶染色的破骨细胞数量和胫骨侵蚀表面的减少相对应。与维生素D活性无关，MBP治疗剂量依赖性地抑制培养骨髓巨噬细胞的破骨细胞生成。当在培养基中加入甲状旁腺激素时，MBP的这些作用被减弱，这与体内观察到的全身性Vdr失活的表型一致，表明严重的甲状旁腺功能亢进限制了MBP在骨中的活性。因此，适应性钙稳态是MBP通过抑制骨吸收发挥保护作用的必要条件。
ObjectivesMilk provide protective effects against bone loss caused by an impaired calcium balance. Although the effects of some elements have previously been confirmed, the involvement of milk basic protein (MBP) in bone mineral metabolism remains poorly characterized. Moreover, the importance of mineral nutrition sufficiency to establish the effect of MBP must be evaluated.MethodsFirst, to evaluate the physiological conditions required for MBP activity, we examined the bone and mineral phenotypes of mice that suffer from insufficient calcium absorption due to a lack of intestinal vitamin D signaling. Second, to determine whether vitamin D signaling affects the effect of MBP on bone resorption, in vitro osteoclastogenesis were assessed using bone marrow cells.ResultsIn mice with systemic vitamin D receptor (Vdr) inactivation, dietary MBP supplementation was unable to normalize hypercalcemia and hyperparathyroidism and failed to rescue bone mineralization impairments. In contrast, calcium and bone homeostasis responded to MBP supplementation when Vdr inactivation was restricted to the intestines. Hyperparathyroidism in intestine-specific Vdr knockout mice was also improved by MBP supplementation, along with a decrease in bone resorption in response to the level of serum tartrate-resistant acid phosphatase 5b. These results corresponded with a reduction in tartrate-resistant acid phosphatase-stained osteoclast numbers and the eroded surface on the tibia. MBP treatment dose-dependently suppressed osteoclastogenesis in cultured bone marrow macrophages regardless of vitamin D activity. These effects of MBP were blunted when parathyroid hormone was added to the culture medium, which is in line with the in vivo phenotype observed with systemic Vdr inactivation and suggests that severe hyperparathyroidism limits MBP activity in the bone.ConclusionsTherefore, adaptive calcium homeostasis is an essential requirement when MBP exerts protective effects through the inhibition of bone resorption.