Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo
Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo
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DOI：
10.1210/en.2005-1020
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Salingcarnboriboon, R;Tsuji, K;Noda, M
卸载引起的骨形成减少的分子机制尚未完全了解。在体外，Runx 2已被认为参与成骨细胞中的机械信号。然而，Runx 2在骨对机械刺激的反应过程中的体内作用尚不清楚。本文的目的是研究Runx 2在体内卸载诱导的骨丢失中的作用。使用9至11周龄Runx 2杂合敲除小鼠（Runx 2（+/-））和野生型（Wt）同窝小鼠进行悬尾2周。骨进行二维显微X射线计算机断层扫描，骨组织形态计量学和RT-PCR分析。Runx 2基因丢失一半剂量加重了骨小梁和皮质包膜中的卸载诱导的骨丢失。与Wt小鼠相比，Runx 2（+/-）小鼠中皮质骨和松质骨中矿物质沉积率和骨形成率的卸载诱导降低加剧。骨吸收参数不受卸载或Runx 2（+/-）基因型的显著影响。在Wt中，骨中的基础Runx 2和osterix mRNA水平降低了50%，而Runx 2（+/-）小鼠的卸载未进一步改变Runx 2和osterix mRNA水平。相反，骨钙素mRNA水平降低卸载，无论Runx 2基因剂量。这些数据表明，在机械卸载或非生理条件下，需要完整的Runx 2基因剂量来维持成骨细胞的正常功能。最后，我们建议Runx 2作为一个关键的靶基因在卸载改变成骨细胞的活性和骨形成在体内。
Molecular mechanisms underlying unloading-induced reduction of bone formation have not yet been fully understood. In vitro, Runx2 has been suggested to be involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in vivo during the bone response to mechanical stimuli have not yet been known. The purpose of this paper was to examine the roles of Runx2 in unloading-induced bone loss in vivo. Tail suspension was conducted for 2 wk using 9- to 11-wk-old Runx2 heterozygous knockout mice (Runx2(+/-)) and wild-type (Wt) littermates. Bones were subjected to two-dimensional micro-x-ray computed tomography, bone histomorphometry and RT-PCR analyses. Loss of half Runx2 gene dosage-exacerbated unloading-induced bone loss in trabecular and cortical envelopes. Unloading-induced reduction in mineral apposition rate and bone formation rate in cortical bone as well as trabecular bone was exacerbated in Runx2(+/-) mice, compared with Wt mice. Bone resorption parameters were not significantly affected by unloading or Runx2(+/-) genotype. Basal Runx2 and osterix mRNA levels in bone were reduced by 50% in Wt, whereas unloading in Runx2(+/-) mice did not further alter Runx2 and osterix mRNA levels. In contrast, osteocalcin mRNA levels were reduced by unloading, regardless of Runx2 gene dosage. These data demonstrated that full Runx2 gene dosage is required for maintaining normal function of osteoblasts in mechanical unloading or nonphysiological condition. Finally, we propose Runx2 as a critical target gene in unloading to alter osteoblastic activity and bone formation in vivo.