Sexual differences in bone porosity, osteocyte density, and extracellular matrix organization due to osteoblastic-specific Bmp2 deficiency in mice.
Sexual differences in bone porosity, osteocyte density, and extracellular matrix organization due to osteoblastic-specific Bmp2 deficiency in mice.
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小鼠中由于成骨细胞特异性Bmp2缺乏导致的骨孔隙率、骨细胞密度和细胞外基质组织的性别差异
DOI：
10.1016/j.bone.2021.116002
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发表时间：
2021-09
期刊：
影响因子：
4.1
通讯作者：
McBride-Gagyi S
中科院分区：
文献类型：
--
作者：
Toth Z;Ward A;Tang SY;McBride-Gagyi S
关于BMP2缺乏与调节骨量和增加骨折风险之间的联系，临床研究得出了相互矛盾的结论。这可能是由于信号蛋白具有性别或年龄相关的效应。以前的临床前研究已经支持了这一作用，但还没有充分确定导致块状材料性质改变的物理机制。本研究在10周龄和15周龄的雄性和雌性小鼠中研究了从成骨细胞系细胞(OSX-Cre；Bmp2fl/fl)去除BMP2的物理效应。对死后收集的骨骼进行断裂韧性测试、参考点压痕测试、显微CT和组织学分析，以确定力学/材料行为与胶原生成、胶原组织和骨结构之间的多尺度关系。BMP2缺失的骨骼更小，更脆，包含更多的腔隙规模的空洞和皮质孔。细胞密度显著增加，通过参考点压痕测量材料水平的差异，与胶原纤维的排列或组织无关。在15周大的雄性中，不同基因型之间的骨骼大小和骨骼断裂韧性的差异尤其显著。总而言之，这项研究表明，BMP2缺乏存在性别和年龄依赖性的影响。来自两性的结果也值得进一步研究BMP2缺乏在成骨细胞向骨细胞转变和整个骨孔洞中的作用。
Clinical studies have come to conflicting conclusions regarding BMP2 deficiency’s link to regulating bone mass and increasing fracture risk. This may be due to the signaling protein having sex- or age-dependent effects. Previous pre-clinical studies have supported a role, but have not adequately determined the physical mechanism causing altered bulk material properties. This study investigated the physical effects of Bmp2 ablation from osteogenic lineage cells (Osx-Cre;Bmp2fl/fl) in 10- and 15-week-old male and female mice. Bones collected post-mortem were subjected to fracture toughness testing, reference point indentation testing, microCT, and histological analysis to determine the multi-scale relationships between mechanical/material behavior and collagen production, collagen organization, and bone architecture. BMP2-deficient bones were smaller, more brittle, and contained more lacunae-scale voids and cortical pores. The cellular density was significantly increased and there were material-level differences measured by reference point indentation, independently of collagen fiber alignment or organization. The disparities in bone size and in bone fracture toughness between genotypes were especially striking in males at 15-weeks-old. Together, this study suggests that there are sex- and age-dependent effects of BMP2 deficiency. The results from both sexes also warrant further investigation into BMP2 deficiency’s role in osteoblasts’ transition to osteocytes and overall bone porosity.
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影响因子：
9.8
作者：
Styrkarsdottir U;Cazier JB;Kong A;Rolfsson O;Larsen H;Bjarnadottir E;Johannsdottir VD;Sigurdardottir MS;Bagger Y;Christiansen C;Reynisdottir I;Grant SF;Jonasson K;Frigge ML;Gulcher JR;Sigurdsson G;Stefansson K
通讯作者：
Stefansson K
影响因子：
2.8
作者：
McBride-Gagyi, Sarah;Toth, Zacharie;Nicolaou, Daemeon
通讯作者：
Nicolaou, Daemeon
影响因子：
3
作者：
Davey, Rachel A.;Clarke, Michele V.;Zajac, Jeffrey D.
通讯作者：
Zajac, Jeffrey D.
影响因子：
4.1
作者：
Knippenberg, Marlene;Helder, Marco N.;Klein-Nulend, Jenneke
通讯作者：
Klein-Nulend, Jenneke
影响因子：
3.7
作者：
McBride SH;McKenzie JA;Bedrick BS;Kuhlmann P;Pasteris JD;Rosen V;Silva MJ
通讯作者：
Silva MJ