Loss of hyaluronan synthases impacts bone morphology, quality, and mechanical properties
Loss of hyaluronan synthases impacts bone morphology, quality, and mechanical properties
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DOI：
10.1016/j.bone.2023.116779
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发表时间：
2023-04-28
期刊：
影响因子：
4.1
通讯作者：
Chan，Deva D.
中科院分区：
文献类型：
--
作者：
Pendyala，Meghana;Stephen，Samuel J.;Chan，Deva D.
透明质酸是一种由三种同工酶（Has 1、Has 2、Has 3）合成的糖胺聚糖，已知在调节骨转换、重塑和矿化方面发挥作用，从而影响骨质量和强度。本研究的目的是表征Has 1或Has 3的缺失如何影响小鼠骨的形态、基质性质和整体强度。从Has 1 −/−、Has 3 −/−和野生型（WT）C57 Bl/6 J雌性小鼠中分离股骨，并使用微计算机断层扫描、共焦拉曼光谱、三点弯曲和纳米压痕进行分析。在测试的三种基因型中，Has 1 −/−骨的横截面积显著降低（p= 0.0002），硬度降低（p= 0.033），矿物-基质比低（p< 0.0001），具有3 −/−骨的刚度显著高于具有3 −/−骨的刚度。（p< 0.0001）和更高的矿物质-基质比（p < 0.0001），但强度（p= 0.0014）和骨矿物质密度（p < 0.0001）低于WT。有趣的是，与WT相比，Has 3的丢失也与显著较低的晚期糖基化终产物积累相关（p= 0.0478）。总之，这些结果首次证明了透明质酸合酶亚型的丧失对皮质骨结构、含量和生物力学的影响。Has 1的丢失影响形态学、矿化和微米级硬度，而Has 3的丢失降低骨矿物质密度并影响有机基质组成，从而影响整个骨力学。这是第一项表征透明质酸酶损失对骨质量影响的研究，表明透明质酸在骨的发育和调节过程中起着重要作用。
Hyaluronan, a glycosaminoglycan synthesized by three isoenzymes (Has1, Has2, Has3), is known to play a role in regulating bone turnover, remodeling, and mineralization, which in turn can affect bone quality and strength. The goal of this study is to characterize how the loss ofHas1orHas3affects the morphology, matrix properties, and overall strength of murine bone. Femora were isolated fromHas1−/−,Has3−/−, and wildtype (WT) C57Bl/6 J female mice and were analyzed using microcomputed-tomography, confocal Raman spectroscopy, three-point bending, and nanoindentation. Of the three genotypes tested,Has1−/−bones demonstrated significantly lower cross-sectional area (p= 0.0002), reduced hardness (p= 0.033), and lower mineral-to-matrix ratio (p< 0.0001).Has3−/−bones had significantly higher stiffness (p< 0.0001) and higher mineral-to-matrix ratio (p < 0.0001) but lower strength (p= 0.0014) and bone mineral density (p < 0.0001) than WT. Interestingly, loss ofHas3was also associated with significantly lower accumulation of advanced glycation end-products than WT (p= 0.0478). Taken together, these results demonstrate, for the first time, the impact of the loss of hyaluronan synthase isoforms on cortical bone structure, content, and biomechanics. Loss ofHas1impacted morphology, mineralization, and micron-level hardness, while loss ofHas3reduced bone mineral density and affected organic matrix composition, impacting whole bone mechanics. This is the first study to characterize the effect of loss of hyaluronan synthases on bone quality, suggesting an essential role hyaluronan plays during the development and regulation of bone.