Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments.
Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments.
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DOI：
10.1016/j.bone.2016.04.022
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发表时间：
2016-07
期刊：
影响因子：
4.1
通讯作者：
Mishina Y
中科院分区：
文献类型：
--
作者：
Zhang Y;McNerny EG;Terajima M;Raghavan M;Romanowicz G;Zhang Z;Zhang H;Kamiya N;Tantillo M;Zhu P;Scott GJ;Ray MK;Lynch M;Ma PX;Morris MD;Yamauchi M;Kohn DH;Mishina Y
骨形态发生蛋白（BMP）信号通路在骨骼发育和新骨形成中起关键作用。然而，我们先前的研究显示BMP信号传导对骨量的负面影响，因为成骨细胞特异性BMP受体（即BMPR1A）的丢失显示小鼠中骨小梁体积和矿物质密度增加。在这里，我们研究了骨质量和生物力学性能的高骨量与BMPR1A缺乏症使用成骨细胞特异性Bmpr1a条件性敲除（cKO）小鼠模型。胶原生化分析显示cKO骨中成熟交联吡啶啉的水平更高，与胶原修饰酶的上调平行。拉曼光谱区分cKO股骨小梁室中成熟与未成熟交联比和矿物质与基质比的增加，但在皮质室中没有。在cKO中，骨小梁或皮质隔室中的矿物结晶度未发生变化。此外，我们通过纳米压痕测试了固有材料特性，发现cKO小梁隔室中的硬度和弹性模量显著较高，但皮质隔室中没有。由于皮质区域较小，皮质隔室的四点弯曲测试显示cKO骨的结构生物力学特性（即强度和刚度）较低。然而，在材料水平上的生物力学性能没有显著差异，这与皮质区室的纳米压痕测试结果一致。这些研究强调了BMPR1A在生理条件下确定骨质量和机械完整性方面的关键作用，对股骨皮质和小梁隔室具有不同的影响。
Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments.