Abstract：
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.
摘要：
成骨细胞的骨形成是通过基于重塑的骨形成(RBBF)和基于建模的骨形成(MBBF)实现的。前者是在破骨细胞骨吸收后发生骨形成以维持骨量和钙稳态。后者是在静止的骨表面上添加新骨基质的时候。施用抗硬化素中和抗体促进卵巢切除大鼠和绝经后妇女的MBBF。然而,在生理条件下，哪种骨骼形成模式主要发生在Sost缺陷小鼠中，还有待阐明。这里,我们显示，在12周龄Sost缺陷小鼠（C57BL/6背景）中，三分之二的骨形成涉及RBBF。显微计算机断层扫描和组织形态学分析表明，Sost-KO小鼠的小梁骨量高于Sost/-小鼠。相比之下,Sost-KO小鼠的破骨细胞数量保持不变，但这些小鼠血清中的骨吸收标志物TRAP5b略高。用抗RANKL抗体处理增加了Sost+/-或Sost-KO小鼠的骨小梁质量。骨形成标记如类骨质表面，矿物并置率，与媒介物处理的Sost+/-小鼠相比,用抗RANKL抗体处理的Sost+/-小鼠中的骨形成速率几乎完全被抑制。在Sost-KO小鼠中,用抗RANKL抗体治疗抑制了这些参数超过一半。这些发现表明，RBBF占Sost+/-小鼠骨形成的大部分，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抗体可用于检测骨小梁上的MBBF。
