Department of Biochemistry and Structural Biology, UT Health, San Antonio, TX, USA.
Department of Physics, Texas A&M International University, Laredo, TX, USA.
Matrix Biol. 2020 Dec;94:95-109. doi: 10.1016/j.matbio.2020.09.002. Epub 2020 Sep 28.
Recent in vitro evidence shows that glycosaminoglycans (GAGs) and proteoglycans (PGs) in bone matrix may functionally be involved in the tissue-level toughness of bone. In this study, we showed the effect of biglycan (Bgn), a small leucine-rich proteoglycan enriched in extracellular matrix of bone and the associated GAG subtype, chondroitin sulfate (CS), on the toughness of bone in vivo, using wild-type (WT) and Bgn deficient mice. The amount of total GAGs and CS in the mineralized compartment of Bgn KO mouse bone matrix decreased significantly, associated with the reduction of the toughness of bone, in comparison with those of WT mice. However, such differences between WT and Bgn KO mice diminished once the bound water was removed from bone matrix. In addition, CS was identified as the major subtype in bone matrix. We then supplemented CS to both WT and Bgn KO mice to test whether supplemental GAGs could improve the tissue-level toughness of bone. After intradermal administration of CS, the toughness of WT bone was greatly improved, with the GAGs and bound water amount in the bone matrix increased, while such improvement was not observed in Bgn KO mice or with supplementation of dermatan sulfate (DS). Moreover, CS supplemented WT mice exhibited higher bone mineral density and reduced osteoclastogenesis. Interestingly, Bgn KO bone did not show such differences irrespective of the intradermal administration of CS. In summary, the results of this study suggest that Bgn and CS in bone matrix play a pivotal role in imparting the toughness to bone most likely via retaining bound water in bone matrix. Moreover, supplementation of CS improves the toughness of bone in mouse models.
最近的体外证据表明，骨基质中的糖胺聚糖（GAGs）和蛋白聚糖（PGs）可能在组织水平上对骨骼的韧性具有功能作用。在这项研究中，我们使用野生型（WT）和缺乏 biglycan（Bgn）的小鼠（Bgn 缺失型，Bgn KO）研究了富含骨细胞外基质的小富含亮氨酸的蛋白聚糖和相关 GAG 亚型硫酸软骨素（CS）对体内骨骼韧性的影响。与 WT 小鼠相比，Bgn KO 小鼠骨基质中总 GAGs 和 CS 含量显著减少，矿化区的 GAGs 和 CS 含量减少与骨骼韧性降低相关。然而，一旦从骨基质中去除结合水，WT 和 Bgn KO 小鼠之间的这种差异就会减少。此外，CS 被鉴定为骨基质中的主要亚型。然后，我们向 WT 和 Bgn KO 小鼠补充 CS，以测试补充 GAG 是否可以改善骨骼的组织水平韧性。CS 经皮给药后，WT 骨骼的韧性大大提高，骨基质中的 GAG 和结合水含量增加，而 Bgn KO 小鼠则没有观察到这种改善，或用硫酸皮肤素（DS）补充也没有改善。此外，CS 补充 WT 小鼠表现出更高的骨密度和减少破骨细胞形成。有趣的是，无论是否经皮给予 CS，Bgn KO 骨骼都没有显示出这种差异。总之，这项研究的结果表明，骨基质中的 Bgn 和 CS 通过保留骨基质中的结合水，对骨骼的韧性起着关键作用。此外，CS 的补充可以改善小鼠模型中骨骼的韧性。
