Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix

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dc.contributor.authorHua, Rui
dc.contributor.authorNi, Qingwen
dc.contributor.authorEliason, Travis D.
dc.contributor.authorHan, Yan
dc.contributor.authorGu, Sumin
dc.contributor.authorNicolella, Daniel P.
dc.contributor.authorWang, Xiaodu
dc.contributor.authorJiang, Jean X.
dc.date.accessioned2021-01-28T18:02:58Z
dc.date.available2021-01-28T18:02:58Z
dc.date.issued2020-09-28
dc.descriptionArticle available from publisher at https://www.sciencedirect.com/science/article/pii/S0945053X20300895?via%3Dihub.
dc.description.abstractRecent 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.en_US
dc.description.departmentMechanical Engineeringen_US
dc.description.sponsorshipThe work was supported by NIH grants, AR076190 to X.W and J.X.J and Welch Foundation grant AQ-1507 to J.X.J.en_US
dc.identifier.citationHua, R., Ni, Q., Eliason, T. D., Han, Y., Gu, S., Nicolella, D. P., ... & Jiang, J. X. (2020). Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix. Matrix Biology, 94, 95-109.en_US
dc.identifier.issn0945-053X
dc.identifier.urihttps://hdl.handle.net/20.500.12588/219
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesMatrix Biology;Vol. 94
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectBiglycanen_US
dc.subjectChondroitin sulfateen_US
dc.subjectBone matrixen_US
dc.subjectBone toughnessen_US
dc.subjectBound wateren_US
dc.titleBiglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrixen_US
dc.typeArticleen_US

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