Roles of Olfactomedin 1 in Muscle and Bone Alterations Induced by Gravity Change in Mice
Roles of Olfactomedin 1 in Muscle and Bone Alterations Induced by Gravity Change in Mice
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DOI：
10.1007/s00223-020-00710-6
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发表时间：
2020-08-01
影响因子：
4.2
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
--
作者：
Shimoide, Takeshi;Kawao, Naoyuki;Kaji, Hiroshi
微重力会导致肌肉和骨骼的流失。虽然我们之前揭示了重力变化通过前庭系统影响小鼠的肌肉和骨骼，但其详细机制尚未阐明。在这项研究中，我们研究了在超重状态下比目鱼肌中表达上调的嗅球蛋白1(OLFM1)在小鼠骨细胞中的作用。前庭损伤显著降低小鼠比目鱼肌中OLFM1的表达，并使超重力条件下小鼠血清OLFM1水平升高。此外，磷脂酰肌醇3-激酶抑制剂拮抗切应力增强的C2C12肌管中OLFM1的表达。关于OLFM1对骨细胞的影响，OLFM1抑制小鼠骨髓细胞和小鼠破骨前细胞RAW264.7的破骨细胞形成。此外，OLFM1抑制小鼠成骨细胞RANKL的表达和核因子-kappaB信号转导。小鼠血清OLFM1水平与比目鱼肌和骨小梁中OLFM1 mRNA水平呈正相关。总之，我们首次发现OLFM1抑制小鼠细胞中破骨细胞的形成和RANKL的表达。
Microgravity causes both muscle and bone loss. Although we previously revealed that gravity change influences muscle and bone through the vestibular system in mice, its detailed mechanism has not been elucidated. In this study, we investigated the roles of olfactomedin 1 (OLFM1), whose expression was upregulated during hypergravity in the soleus muscle, in mouse bone cells. Vestibular lesion significantly blunted OLFM1 expression in the soleus muscle and serum OLFM1 levels enhanced by hypergravity in mice. Moreover, a phosphatidylinositol 3-kinase inhibitor antagonized shear stress-enhanced OLFM1 expression in C2C12 myotubes. As for the effects of OLFM1 on bone cells, OLFM1 inhibited osteoclast formation from mouse bone marrow cells and mouse preosteoclastic RAW264.7 cells. Moreover, OLFM1 suppressed RANKL expression and nuclear factor-kappa B signaling in mouse osteoblasts. Serum OLFM1 levels were positively related to OLFM1 mRNA levels in the soleus muscle and trabecular bone mineral density of mice. In conclusion, we first showed that OLFM1 suppresses osteoclast formation and RANKL expression in mouse cells.