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-κB 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.

微重力会导致肌肉和骨骼损失。尽管我们先前曾揭示重力变化会通过小鼠的前庭系统影响肌肉和骨骼，但其详细机制尚未阐明。在这项研究中，我们调查了olfactomedin 1（OLFM1）的作用，该比表达在比目鱼肌超重力过程中在小鼠骨骼细胞中表达上调。前庭病变明显使比目鱼肌中的OLFM1表达变钝，而小鼠的超重力增强了血清OLFM1的水平。此外，磷脂酰肌醇3-激酶抑制剂可拮抗C2C12肌管中剪切应力增强的OLFM1表达。至于OLFM1对骨细胞的作用，OLFM1抑制了小鼠骨髓细胞和小鼠破骨前RAW264.7细胞的破骨细胞形成。此外，OLFM1抑制小鼠成骨细胞中的RANKL表达和核因子-κB信号传导。小鼠比目鱼肌和小梁骨矿物质密度与血清OLFM1水平呈正相关。总之，我们首先显示OLFM1抑制小鼠细胞中的破骨细胞形成和RANKL表达。