Sclerostin expression in trabecular bone is downregulated by osteoclasts
Sclerostin expression in trabecular bone is downregulated by osteoclasts
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DOI：
10.1038/s41598-020-70817-1
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发表时间：
2020-08-13
影响因子：
4.6
通讯作者：
Kobayashi, Yasuhiro
中科院分区：
文献类型：
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作者：
Koide, Masanori;Yamashita, Teruhito;Kobayashi, Yasuhiro
骨组织有骨周转率高的骨小梁骨和骨周转率低的皮质骨。确定这些骨组织周转率的机制尚不清楚。骨细胞分泌硬化蛋白，一种Wnt/ β -连环蛋白信号拮抗剂，并抑制骨形成。我们发现Sost报告小鼠皮质骨中的硬化蛋白表达比小梁骨中的更明显。据报道，破骨细胞分泌的白血病抑制因子（LIF）抑制硬化蛋白的表达，促进骨形成。在这里，我们报道破骨细胞下调骨小梁中硬化蛋白的表达并促进骨更新。用抗rankl抗体处理C57BL/6小鼠，可消除骨小梁内破骨细胞和lif阳性细胞的数量。骨小梁内硬化蛋白阳性细胞增多，β -catenin阳性细胞增多，骨形成减少。此外，Tnfsf11杂合（Rankl(+/-)）小鼠的骨小梁中lif阳性细胞数量减少，硬化蛋白阳性细胞数量增加。Rankl（+/-）小鼠表现出β -catenin阳性细胞数量减少，骨小梁骨形成减少。此外，在培养的破骨细胞中，RANKL刺激增加了Lif mRNA的表达，表明RANKL信号增加了Lif的表达。综上所述，破骨细胞下调硬化蛋白表达，促进骨小梁骨转换。
Bone tissues have trabecular bone with a high bone turnover and cortical bone with a low turnover. The mechanisms by which the turnover rate of these bone tissues is determined remain unclear. Osteocytes secrete sclerostin, a Wnt/beta -catenin signaling antagonist, and inhibit bone formation. We found that sclerostin expression in cortical bone is more marked than in trabecular bone in Sost reporter mice. Leukemia inhibitory factor (LIF) secreted from osteoclasts reportedly suppressed sclerostin expression and promoted bone formation. Here, we report that osteoclasts downregulate sclerostin expression in trabecular bone and promote bone turnover. Treatment of C57BL/6 mice with an anti-RANKL antibody eliminated the number of osteoclasts and LIF-positive cells in trabecular bone. The number of sclerostin-positive cells was increased in trabecular bone, while the number of beta -catenin-positive cells and bone formation were decreased in trabecular bone. Besides, Tnfsf11 heterozygous (Rankl(+/-)) mice exhibited a decreased number of LIF-positive cells and increased number of sclerostin-positive cells in trabecular bone. Rankl(+/-) mice exhibited a decreased number of beta -catenin-positive cells and reduced bone formation in trabecular bone. Furthermore, in cultured osteoclasts, RANKL stimulation increased Lif mRNA expression, suggesting that RANKL signal increased LIF expression. In conclusion, osteoclasts downregulate sclerostin expression and promote trabecular bone turnover.