Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix.
Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix.
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DOI：
10.1016/j.matbio.2020.09.002
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Jiang JX
中科院分区：
文献类型：
--
作者：
Hua R;Ni Q;Eliason TD;Han Y;Gu S;Nicolella DP;Wang X;Jiang JX
最近的体外研究表明，骨基质中的糖胺多聚糖(GAG)和蛋白多聚糖(PGs)可能在功能上参与了骨组织水平的韧性。在本研究中，我们利用野生型(WT)和BGN缺陷小鼠，研究了富含亮氨酸的小分子蛋白多糖BGN(BGN)及其相关的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小鼠骨基质矿化室中总GAG和CS的含量显著减少，并伴随着骨韧性的降低。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缩小。此外，CS是骨基质中的主要亚型。然后，我们向WT和BGN KO小鼠添加CS，以测试补充GAG是否可以改善骨的组织水平的韧性。皮内注射CS后，WT骨的韧性显著提高，骨基质中的GAG和结合水含量增加，而BGN KO小鼠和补充硫酸皮肤素(DS)的小鼠未见这种改善。此外，添加CS的WT小鼠表现出更高的骨密度和更少的破骨细胞生成。有趣的是，无论皮内注射CS，BGN KO骨并没有表现出这样的差异。综上所述，本研究结果提示，骨基质中的BGN和CS很可能是通过保留骨基质中的结合水来增强骨的韧性的。此外，补充壳聚糖能提高小鼠骨骼的韧性。
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.
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影响因子：
6.2
作者：
Chen, XD;Shi, ST;Young, MF
通讯作者：
Young, MF
影响因子：
3.4
作者：
Han, EunHee;Chen, Silvia S.;Sah, Robert L.
通讯作者：
Sah, Robert L.
影响因子：
6.2
作者：
Corsi, A;Xu, T;Young, MF
通讯作者：
Young, MF
影响因子：
4.1
作者：
HILDEBRAND, A;ROMARIS, M;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
4.2
作者：
HASHIMOTO, Y;LESTER, GE;YAMAUCHI, M
通讯作者：
YAMAUCHI, M