Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Molecules. 2018 Jun 23;23(7):1517. doi: 10.3390/molecules23071517.
Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of , which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of , and decreased ratio of compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of . In contrast, was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.
最近的研究表明，共生菌群不仅通过正向调节破骨细胞活性影响宿主的能量代谢和免疫发育，而且还影响骨重塑。然而，共生菌群调节骨细胞的机制尚未阐明。在这项研究中，比较了 8 周龄的无菌（SPF）和无菌（GF）小鼠的肺泡骨和颅骨分离的原代成骨细胞。微 CT 分析显示，与 GF 小鼠相比，SPF 小鼠具有更大的体型，与较低的牙槽骨骨密度和骨体积分数相关。在 SPF 小鼠中观察到更多的破骨细胞在牙槽骨中，以及更高的抗酒石酸酸性磷酸酶 5b 血清水平。来自 SPF 牙槽骨的组织提取物显示更高水平的组织蛋白酶 K，表明破骨细胞活性更高。与 GF 小鼠相比，SPF 肺泡提取物还显示出更高水平的γ-羧基谷氨酸-骨钙素作为成熟成骨细胞的标志物。直接从牙槽骨中分离的 RNA 的聚合酶链反应（PCR）阵列分析显示，在 SPF 小鼠中，与 GF 小鼠相比， 的 mRNA 表达强烈增强， 也作为骨矿化抑制剂起作用。与 GF 小鼠相比，来自 SPF 小鼠的颅骨培养成骨细胞的矿化减少，但 和 的 mRNA 表达显著增强， 的比例降低。此外，培养的颅骨成骨细胞中转录因子的 PCR 阵列分析显示， 的表达强烈上调。相反， 在 SPF 成骨细胞中强烈下调。这些结果表明，共生菌群通过刺激成骨细胞中骨钙素的表达来防止过度矿化，并通过调节特定的转录因子来增强成骨细胞和破骨细胞的活性。
