Osteoprotegerin Deficiency Results in Disruption of Posterofrontal Suture Closure in Mice: Implications in Nonsyndromic Craniosynostosis
Osteoprotegerin Deficiency Results in Disruption of Posterofrontal Suture Closure in Mice: Implications in Nonsyndromic Craniosynostosis
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DOI：
10.1097/prs.0000000000001284
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Reid, Russell R.
中科院分区：
文献类型：
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作者：
Beederman, Maureen;Kim, Stephanie H.;Reid, Russell R.
背景：破骨细胞在颅缝融合中的作用知之甚少。破骨细胞主要受核因子-kappaB受体激活剂和核因子-kappaB配体受体激活剂的调节，两者都能促进破骨细胞的分化、激活和存活；而骨保护素是核因子kappa B受体激活剂的可溶性抑制物。作者的工作利用基因敲除技术研究了骨保护素在这一过程中的作用。方法：对野生型、骨保护素杂合子和骨保护素基因敲除小鼠在3、5、7、9和16周进行连续显微计算机断层扫描。在同一时间点进行缝合密度测量和颅骨测量分析。结果：骨保护素基因敲除小鼠的前额后缝线融合程度明显低于野生型和杂合子小鼠。骨保护素缺乏导致基因敲除小鼠的骨缝骨密度显著降低。野生型和骨保护素基因敲除小鼠之间的非缝合颅骨密度没有降低。缝合切片的组织化学支持这些微型计算机断层扫描的发现。最后，骨保护素基因敲除的小鼠在所有时间点都减少了前后位颅骨距离，在16周的时间点增加了眶间距离。结论：作者的数据表明，骨保护素表达的扰动和随后的破骨细胞形成的变化导致了小鼠颅缝和额后缝的形态变化。
Background: Little is known about the role of osteoclasts in cranial suture fusion. Osteoclasts are predominantly regulated by receptor activator of nuclear factor kappa B and receptor activator of nuclear factor kappa B ligand, both of which lead to osteoclast differentiation, activation, and survival; and osteoprotegerin, a soluble inhibitor of receptor activator of nuclear factor kappa B. The authors' work examines the role of osteoprotegerin in this process using knockout technology.Methods: Wild-type, osteoprotegerin-heterozygous, and osteoprotegerin-knockout mice were imaged by serial micro-computed tomography at 3, 5, 7, 9, and 16 weeks. Suture density measurements and craniometric analysis were performed at these same time points. Posterofrontal sutures were harvested from mice after the week-16 time point and analyzed by means of histochemistry.Results: Micro-computed tomographic analysis of the posterofrontal suture revealed reduced suture fusion in osteoprotegerin-knockout mice compared with wild-type and heterozygous littermates. Osteoprotegerin deficiency resulted in a statistically significant decrease in suture bone density in knockout mice. There was no reduction in the density of non-suture-containing calvarial bone between wild-type and osteoprotegerin-knockout mice. Histochemistry of suture sections supported these micro-computed tomographic findings. Finally, osteoprotegerin-knockout mice had reduced anteroposterior skull distance at all time points and an increased interorbital distance at the week-16 time point.Conclusion: The authors' data suggest that perturbations in the expression of osteoprotegerin and subsequent changes in osteoclastogenesis lead to alterations in murine cranial and posterofrontal suture morphology.