Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan.
Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan; Department of Orthopaedic Surgery, Kindai University Faculty of Medicine, Osakasayama, Japan.
Bone. 2024 Apr;181:117040. doi: 10.1016/j.bone.2024.117040. Epub 2024 Feb 4.
The intermittent administration of parathyroid hormone (PTH) exerts potent bone anabolic effects, which increase bone mineral density (BMD) and reduce fracture risk in osteoporotic patients. However, the underlying mechanisms remain unclear. Tmem119 has been proposed as a factor that is closely linked to the osteoblast phenotype, and we previously reported that PTH enhanced the expression of Tmem119 in mouse osteoblastic cells. However, roles of Tmem119 in the bone anabolic effects of PTH in vivo remain unknown. We herein investigated the roles of Tmem119 in bone anabolic effects of PTH using Tmem119-deficient mice. Tmem119 deficiency significantly reduced PTH-induced increases in trabecular bone volume and cortical BMD of femurs. Effects of Tmem119 deficiency on bone mass seemed predominant in female mice. Histomorphometric analyses with calcein labeling showed that Tmem119 deficiency significantly attenuated PTH-induced increases in the rates of bone formation and mineralization as well as numbers of osteoblasts. Moreover, Tmem119 deficiency significantly blunted PTH-induced decreases in phosphorylation of β-catenin and increases in alkaline phosphatase activity in osteoblasts. In conclusion, the present results indicate that Tmem119 is involved in bone anabolic effects of PTH through osteoblastic bone formation partly related to canonical Wnt-β-catenin signaling in mice.
甲状旁腺激素（PTH）的间歇性给药具有强大的骨合成代谢作用，可增加骨质疏松症患者的骨矿物质密度（BMD）并降低骨折风险。然而，其潜在机制尚不清楚。Tmem119 被提出是与成骨细胞表型密切相关的因素，我们之前报道 PTH 增强了小鼠成骨细胞中 Tmem119 的表达。然而，Tmem119 在 PTH 体内骨合成代谢作用中的作用尚不清楚。我们使用 Tmem119 缺陷小鼠研究了 Tmem119 在 PTH 骨合成代谢作用中的作用。Tmem119 缺陷显著降低了 PTH 诱导的股骨小梁骨体积和皮质 BMD 的增加。Tmem119 缺陷对骨量的影响在雌性小鼠中似乎更为明显。用 calcein 标记进行组织形态计量学分析表明，Tmem119 缺陷显著减弱了 PTH 诱导的骨形成和矿化率以及成骨细胞数量的增加。此外，Tmem119 缺陷显著抑制了 PTH 诱导的成骨细胞中β-连环蛋白磷酸化的降低和碱性磷酸酶活性的增加。总之，本研究结果表明，Tmem119 通过成骨细胞的骨形成参与了 PTH 的骨合成代谢作用，部分与小鼠中的经典 Wnt-β-连环蛋白信号通路有关。
