Ishijima Muneaki, Tsuji Kunikazu, Rittling Susan R, Yamashita Teruhito, Kurosawa Hisashi, Denhardt David T, Nifuji Akira, Ezura Yoichi, Noda Masaki
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10, Kanda-Surugadai 2-Chome, Tokyo, Japan.
J Endocrinol. 2007 May;193(2):235-43. doi: 10.1677/joe.1.06704.
Mechanical stress to bone plays a crucial role in the maintenance of bone homeostasis. It causes the deformation of bone matrix and generates strain force, which could initiate the mechano-transduction pathway. The presence of osteopontin (OPN), which is one of the abundant proteins in bone matrix, is required for the effects of mechanical stress on bone, as we have reported that OPN-null (OPN-/-) mice showed resistance to unloading-induced bone loss. However, cellular mechanisms underlying the phenomenon have not been completely elucidated. To obtain further insight into the role of OPN in mediating mechanical stress effect on bone, we examined in vitro mineralization and osteoclast-like cell formation in bone marrow cells obtained from hind limb bones of OPN-/- mice after tail suspension. The levels of mineralized nodule formation of bone marrow cells derived from the femora subjected to unloading were decreased compared with that from loaded control in wild-type mice. However, these were not decreased in cells from OPN-/- mice after tail suspension compared with that from loaded OPN-/- mice. Moreover, while spreading of osteoclast-like cells derived from bone marrow cells of the femora subjected to unloading was enhanced compared with that from loaded control in wild-type mice, this enhancement of spreading of these cells derived from the femora subjected to unloading was not recognized compared with those from loaded control in OPN-/- mice. These data provided cellular bases for the effect of the OPN deficiency on in vitro reduced mineralized nodule formation by osteoblasts and on enhancement of osteoclast spreading in vitro induced by the absence of mechanical stress. These in vitro results correlate well with the resistance to unloading-induced bone loss in OPN-/- mice in vivo, suggesting that OPN has an important role in the effects of unloading-induced alterations of differentiation of bone marrow into osteoblasts and osteoclasts.
骨骼所受的机械应力在维持骨稳态中起着至关重要的作用。它会导致骨基质变形并产生应变力，进而启动机械转导通路。骨桥蛋白（OPN）是骨基质中含量丰富的蛋白质之一，机械应力对骨骼产生影响需要有OPN的存在，因为我们曾报道OPN基因敲除（OPN-/-）小鼠对卸载诱导的骨质流失具有抗性。然而，这一现象背后的细胞机制尚未完全阐明。为了进一步深入了解OPN在介导机械应力对骨骼影响中的作用，我们检测了尾悬吊后从OPN-/-小鼠后肢骨骼获取的骨髓细胞的体外矿化及破骨细胞样细胞形成情况。与野生型小鼠中加载对照组的股骨来源骨髓细胞相比，卸载后股骨来源的骨髓细胞矿化结节形成水平降低。然而，尾悬吊后OPN-/-小鼠的细胞与加载的OPN-/-小鼠相比，这些水平并未降低。此外，与野生型小鼠中加载对照组相比，卸载后股骨来源的骨髓细胞衍生的破骨细胞样细胞铺展增强，但与OPN-/-小鼠中加载对照组相比，卸载后股骨来源的这些细胞的铺展增强并未被观察到。这些数据为OPN缺乏对成骨细胞体外矿化结节形成减少以及对机械应力缺失诱导的破骨细胞体外铺展增强的影响提供了细胞基础。这些体外结果与OPN-/-小鼠体内对卸载诱导的骨质流失的抗性密切相关，表明OPN在卸载诱导的骨髓向成骨细胞和破骨细胞分化改变的影响中具有重要作用。
