Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
J Cell Biochem. 2011 Dec;112(12):3525-30. doi: 10.1002/jcb.23327.
Loss of mechanical stress or unloading causes disuse osteoporosis that leads to fractures and deteriorates body function and affects mortality rate in aged population. This bone loss is due to reduction in osteoblastic bone formation and increase in osteoclastic bone resorption. MuRF1 is a muscle RING finger protein which is involved in muscle wasting and its expression is enhanced in the muscle of mice subjected to disuse condition such as hind limb unloading (HU). However, whether MuRF1 is involved in bone loss due to unloading is not known. We therefore examined the effects of MuRF1 deficiency on unloading-induced bone loss. We conducted hind limb unloading of MuRF1 KO mice and wild-type control mice. Unloading induced about 60% reduction in cancellous bone volume (BV/TV) in WT mice. In contrast, MuRF1 deficiency suppressed unloading-induced cancellous bone loss. The cortical bone mass was also reduced by unloading in WT mice. In contrast, MuRF1 deficiency suppressed this reduction in cortical bone mass. To understand whether the effects of MuRF1 deficiency suppress bone loss is on the side of bone formation or bone resorption, histomorphometry was conducted. Unloading reduced bone osteoblastic formation rate (BFR) in WT. In contrast, MuRF1 deficiency suppressed this reduction. Regarding bone resorption, unloading increased osteoclast number in WT. In contrast, MURF1 deficiency suppressed this osteoclast increase. These data indicated that the ring finger protein, MURF1 is involved in disuse-induced bone loss in both of the two major bone remodeling activities, osteoblastic bone formation and osteoclastic bone resorption.
失去机械应力或废用会导致废用性骨质疏松症，导致骨折，恶化身体功能，并影响老年人群的死亡率。这种骨丢失是由于成骨细胞骨形成减少和破骨细胞骨吸收增加所致。MuRF1 是一种肌肉环指蛋白，参与肌肉减少，在经历废用状态（如后肢去负荷）的小鼠肌肉中其表达增强。然而，MuRF1 是否参与废用引起的骨丢失尚不清楚。因此，我们研究了 MuRF1 缺失对废用引起的骨丢失的影响。我们对 MuRF1 KO 小鼠和野生型对照小鼠进行了后肢去负荷。去负荷导致 WT 小鼠松质骨体积（BV/TV）减少约 60%。相比之下，MuRF1 缺失抑制了去负荷引起的松质骨丢失。WT 小鼠的皮质骨量也因去负荷而减少。相比之下，MuRF1 缺失抑制了这种皮质骨量的减少。为了了解 MuRF1 缺失抑制骨丢失的作用是在骨形成还是骨吸收方面，进行了组织形态计量学研究。去负荷降低了 WT 中骨形成率（BFR）。相比之下，MuRF1 缺失抑制了这种减少。关于骨吸收，去负荷增加了 WT 中的破骨细胞数量。相比之下，MuRF1 缺失抑制了这种破骨细胞的增加。这些数据表明，环指蛋白 MuRF1 参与了两种主要的骨重建活动（成骨细胞骨形成和破骨细胞骨吸收）中的废用性骨丢失。
