Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan.
Department of Operative Dentistry, Endodontology and Periodontology, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan.
Bone. 2022 Jul;160:116401. doi: 10.1016/j.bone.2022.116401. Epub 2022 Apr 3.
Bone formation by osteoblasts is achieved through remodeling-based bone formation (RBBF) and modeling-based bone formation (MBBF). The former is when bone formation occurs after osteoclastic bone resorption to maintain bone mass and calcium homeostasis. The latter is when new bone matrices are added on the quiescent bone surfaces. Administration of anti-sclerostin neutralizing antibody promotes MBBF in ovariectomized rats and postmenopausal women. However, it remains to be elucidated which mode of bone formation mainly occurs in Sost-deficient mice under physiological conditions. Here, we show that two-thirds of bone formation involves RBBF in 12-week-old Sost-deficient mice (C57BL/6 background). Micro-computed tomography and histomorphometric analyses showed that the trabecular bone mass in Sost-KO mice was higher than that in Sost mice. In contrast, the osteoclast number remained unchanged in Sost-KO mice, but the bone resorption marker TRAP5b in serum was slightly higher in those mice. Treatment with anti-RANKL antibody increased the trabecular bone mass of Sost or Sost-KO mice. Bone formation markers such as osteoid surfaces, the mineral apposition rate, and bone formation rate were almost completely suppressed in Sost mice treated with anti-RANKL antibody compared with vehicle-treated Sost mice. In Sost-KO mice, treatment with anti-RANKL antibody suppressed those parameters by more than half. These findings indicate that RBBF accounts for most of the bone formation in Sost mice, whereas approximately two-thirds of bone formation is estimated to be remodeling-based in 12-week-old Sost-deficient mice. Furthermore, anti-RANKL antibody may be useful for detecting MBBF on trabecular bone.
成骨细胞通过基于重塑的骨形成 (RBBF) 和基于建模的骨形成 (MBBF) 来实现骨形成。前者是指在破骨细胞进行骨吸收以维持骨量和钙平衡后发生的骨形成。后者是指在静止的骨表面添加新的骨基质。抗硬化素中和抗体的给药促进去卵巢大鼠和绝经后妇女的 MBBF。然而，在生理条件下，Sost 缺陷小鼠中哪种骨形成方式主要发生仍有待阐明。在这里，我们表明，在 12 周龄的 Sost 缺陷小鼠（C57BL/6 背景）中，有三分之二的骨形成涉及 RBBF。微计算机断层扫描和组织形态计量学分析表明，Sost-KO 小鼠的小梁骨量高于 Sost 小鼠。相比之下，Sost-KO 小鼠中的破骨细胞数量保持不变，但这些小鼠的血清中破骨细胞吸收标志物 TRAP5b 略高。用抗 RANKL 抗体治疗可增加 Sost 或 Sost-KO 小鼠的小梁骨量。与用载体处理的 Sost 小鼠相比，用抗 RANKL 抗体处理的 Sost 小鼠的骨形成标志物，如类骨质表面、矿化速率和骨形成速率几乎完全受到抑制。在 Sost-KO 小鼠中，用抗 RANKL 抗体治疗抑制了这些参数的一半以上。这些发现表明，RBBF 占 Sost 小鼠中大部分骨形成，而在 12 周龄的 Sost 缺陷小鼠中，大约三分之二的骨形成估计是基于重塑的。此外，抗 RANKL 抗体可能有助于检测小梁骨上的 MBBF。
