Parathyroid hormone (PTH) is a critical regulator of skeletal development that promotes both bone formation and bone resorption. Using microbiota depletion by wide-spectrum antibiotics and germ-free (GF) female mice, we showed that the microbiota was required for PTH to stimulate bone formation and increase bone mass. Microbiota depletion lowered butyrate levels, a metabolite responsible for gut-bone communication, while reestablishment of physiologic levels of butyrate restored PTH-induced anabolism. The permissive activity of butyrate was mediated by GPR43 signaling in dendritic cells and by GPR43-independent signaling in T cells. Butyrate was required for PTH to increase the number of bone marrow (BM) regulatory T cells (Tregs). Tregs stimulated production of the osteogenic Wnt ligand Wnt10b by BM CD8+ T cells, which activated Wnt-dependent bone formation. Together, these data highlight the role that butyrate produced by gut luminal microbiota plays in triggering regulatory pathways, which are critical for the anabolic action of PTH in bone.

中文翻译：

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甲状旁腺激素依赖性骨形成需要肠道微生物群产生丁酸盐。

甲状旁腺激素 (PTH) 是骨骼发育的关键调节剂，可促进骨形成和骨吸收。通过广谱抗生素和无菌 (GF) 雌性小鼠消耗微生物群，我们发现微生物群是 PTH 刺激骨形成和增加骨量所必需的。微生物群耗尽降低了丁酸盐水平，丁酸盐是一种负责肠骨通讯的代谢物，而丁酸盐生理水平的重建恢复了 PTH 诱导的合成代谢。丁酸盐的允许活性由树突状细胞中的 GPR43 信号和 T 细胞中的 GPR43 独立信号介导。PTH 需要丁酸盐来增加骨髓 (BM) 调节性 T 细胞 (Treg) 的数量。Tregs 刺激 BM CD8+ T 细胞产生成骨 Wnt 配体 Wnt10b，这激活了 Wnt 依赖性骨形成。总之，这些数据突出了肠腔微生物群产生的丁酸在触发调节通路中的作用，这对于 PTH 在骨骼中的合成代谢作用至关重要。