TY - JOUR
T1 - Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix
AU - Hua, Rui
AU - Ni, Qingwen
AU - Eliason, Travis D.
AU - Han, Yan
AU - Gu, Sumin
AU - Nicolella, Daniel P.
AU - Wang, Xiaodu
AU - Jiang, Jean X.
N1 - Funding Information:
The authors thank Dr. Marian Young at the National Institute of Dental and Craniofacial Research, National Institutes of Health for generously providing biglycan knockout mice, Hongyun Cheng for techical assistance and Eduardo R. Cardenas for critical reading of the manuscript. The work was supported by NIH grants, AR076190 to X.W and J.X.J and Welch Foundation grant AQ-1507 to J.X.J.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Biglycan
KW - Bone matrix
KW - Bone toughness
KW - Bound water
KW - Chondroitin sulfate
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U2 - 10.1016/j.matbio.2020.09.002
DO - 10.1016/j.matbio.2020.09.002
M3 - Article
AN - SCOPUS:85092221688
VL - 94
SP - 95
EP - 109
JO - Matrix Biology
JF - Matrix Biology
SN - 0945-053X
ER -