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 (GAG) 和蛋白聚糖 (PG) 可能在功能上参与骨的组织水平韧性。在这项研究中，我们展示了双糖链蛋白聚糖 (Bgn)，一种富含骨细胞外基质的富含亮氨酸的小蛋白聚糖和相关的 GAG 亚型硫酸软骨素 (CS) ，使用野生型在体内对骨骼韧性的影响。(WT) 和Bgn缺陷小鼠。与 WT 小鼠相比，Bgn KO 小鼠骨基质矿化区室中 GAG 和 CS 的总量显着减少，这与骨韧性的降低有关。然而，WT和Bgn之间的这种差异一旦从骨基质中去除结合水，KO小鼠就会减少。此外，CS 被确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皮内给药后，WT骨的韧性大大提高，骨基质中GAGs和结合水量增加，而在Bgn KO小鼠或补充硫酸皮肤素（DS）中未观察到这种改善。此外，补充了 CS 的 WT 小鼠表现出更高的骨矿物质密度和减少的破骨细胞生成。有趣的是，Bgn无论 CS 的皮内给药如何，KO 骨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 在最有可能通过保留骨基质中的结合水来赋予骨骼韧性方面发挥着关键作用。此外，CS 的补充提高了小鼠模型中骨骼的韧性。