Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
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DOI：
10.1371/journal.pone.0096862
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Silva MJ
中科院分区：
文献类型：
--
作者：
McBride SH;McKenzie JA;Bedrick BS;Kuhlmann P;Pasteris JD;Rosen V;Silva MJ
骨形态发生蛋白2（BMP 2）在骨骼中的重要性是众所周知的。BMP 2在发育、生长和愈合过程中在多种组织中表达。在这项研究中，我们试图更好地确定组织特异性BMP 2在出生后生长过程中的作用，并确定BMP 2敲除是否影响终末分化细胞创造高质量骨材料的能力。我们将BMP 2敲除靶向两种已知在生长和愈合过程中表达BMP 2的分化细胞类型，即早期成骨细胞及其后代（osterix促进Cre）和血管内皮细胞（血管内皮钙粘蛋白促进Cre）。我们的目标是评估产后骨骼生长、结构和强度。我们假设从成骨细胞和血管细胞（分别）中去除BMP 2将导致骨骼变小，骨材料性能变差。在12周龄和24周龄时，BMP 2的成骨细胞敲除使体重减轻了20%，但血管敲除没有影响。对胫骨骨的分析显示，在成骨细胞敲除中皮质骨和松质骨的大小和体积减少，但在血管内皮敲除中没有。此外，前肢力量测试显示，在BMP 2的成骨细胞敲除中，在12周和24周时极限力均降低30%，但在血管内皮敲除中没有变化。此外，成骨细胞敲除小鼠股骨的机械强度测试表明，在12和24周龄时，杨氏模量增加（大于35%），但屈服后位移减少（大于50%）。总之，BMP 2的成骨细胞敲除在全骨和材料水平上减小了骨尺寸并改变了机械性能。成骨细胞来源的BMP 2在出生后骨骼的生长、结构和强度中具有重要作用，而血管内皮来源的BMP 2则没有。
The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young’s modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not.
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血管组织是在分散骨质发生引起的骨形成过程中BMP2表达的主要来源。
影响因子：
4.1
作者：
Matsubara, Hidenori;Hogan, Daniel E.;Morgan, Elise F.;Mortlock, Douglas P.;Einhorn, Thomas A.;Gerstenfeld, Louis C.
通讯作者：
Gerstenfeld, Louis C.
影响因子：
3.7
作者：
Chen J;Li L;Su J;Li B;Chen T;Wong YS
通讯作者：
Wong YS
影响因子：
2.5
作者：
Alva, JA;Zovein, AC;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
4.1
作者：
Martinez, Mario D.;Schmid, Gregory J.;McKenzie, Jennifer A.;Ornitz, David M.;Silva, Matthew J.
通讯作者：
Silva, Matthew J.
影响因子：
6.2
作者：
Devlin, Maureen J.;Cloutier, Alison M.;Thomas, Nishina A.;Panus, David A.;Lotinun, Sutada;Pinz, Ilka;Baron, Roland;Rosen, Clifford J.;Bouxsein, Mary L.
通讯作者：
Bouxsein, Mary L.