{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:25Z","timestamp":1785413665119,"version":"3.56.0"},"reference-count":163,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["T32TR004544"],"award-info":[{"award-number":["T32TR004544"]}]},{"award":["T32TR004544"],"award-info":[{"award-number":["T32TR004544"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health","award":["R01AR076190"],"award-info":[{"award-number":["R01AR076190"]}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["AQ-1507"],"award-info":[{"award-number":["AQ-1507"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"award":["AQ-1507"],"award-info":[{"award-number":["AQ-1507"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Clinically, bone mineral density (BMD) accounts for only approximately 50% of the observed variance in bone fragility fractures. This review examines the dynamic and mechanistic role of the non-collagenous organic matrix, specifically proteoglycans (PGs) and glycosaminoglycans (GAGs), in maintaining bone toughness and bone quality. During aging, bulk cortical GAG levels decrease by up to ~17% and are highly associated with reduced bone tissue toughness. We analyze how this age-related loss may arise from uncoupled bone remodeling and tissue aging, including the accumulation of older, interstitial tissue and dysregulated osteocyte-mediated matrix maintenance. We then discuss the functional importance of PG\/GAG composition, maturation, and catabolism and how perturbations in these processes can promote pro-inflammatory signaling that accelerates matrix degradation and contributes to systemic aging. Lastly, we discuss potential interventions to preserve or restore GAGs\/PGs in bone and improve overall bone quality.<\/jats:p>","DOI":"10.3390\/biom16040572","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:38:26Z","timestamp":1776080306000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteoglycan Dynamics and Bone Quality: Molecular Regulation to Age-Related Fragility"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-6624","authenticated-orcid":false,"given":"Savannah","family":"Heath","sequence":"first","affiliation":[{"name":"Biochemistry and Structural Biology Department, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6686-6913","authenticated-orcid":false,"given":"Rui","family":"Hua","sequence":"additional","affiliation":[{"name":"Biochemistry and Structural Biology Department, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-1278","authenticated-orcid":false,"given":"Xiaodu","family":"Wang","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Department, University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-5716","authenticated-orcid":false,"given":"Jean","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biochemistry and Structural Biology Department, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1016\/j.jmbbm.2011.05.020","article-title":"Effect of aging on the transverse toughness of human cortical bone: Evaluation by R-curves","volume":"4","author":"Koester","year":"2011","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.bone.2004.02.001","article-title":"On the origin of the toughness of mineralized tissue: Microcracking or crack bridging?","volume":"34","author":"Nalla","year":"2004","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S8756-3282(98)00071-4","article-title":"Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties","volume":"23","author":"Wang","year":"1998","journal-title":"Bone"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2106\/00004623-199703000-00016","article-title":"Age-related changes in the compressive strength of cancellous bone. The relative importance of changes in density and trabecular architecture","volume":"79","author":"McCalden","year":"1997","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.2106\/00004623-199308000-00009","article-title":"Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure","volume":"75","author":"McCalden","year":"1993","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_6","first-page":"46","article-title":"An overview and management of osteoporosis","volume":"4","year":"2017","journal-title":"Eur. J. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1111\/j.1532-5415.1993.tb07307.x","article-title":"Type of fall and risk of hip and wrist fractures: The study of osteoporotic fractures. The Study of Osteoporotic Fractures Research Group","volume":"41","author":"Nevitt","year":"1993","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1148\/radiology.160.2.3726129","article-title":"Bone mineral content in early-postmenopausal and postmenopausal osteoporotic women: Comparison of measurement methods","volume":"160","author":"Reinbold","year":"1986","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/00003086-198802000-00035","article-title":"Bone mineral content and mechanical strength. An ex vivo study on human femora at autopsy","volume":"227","author":"Alho","year":"1988","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1007\/BF01673423","article-title":"Architecture and vertebral fracture","volume":"53","author":"Recker","year":"1993","journal-title":"Calcif. Tissue Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1172\/JCI113523","article-title":"Age and bone mass as predictors of fracture in a prospective study","volume":"81","author":"Hui","year":"1988","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00198-007-0543-5","article-title":"FRAX and the assessment of fracture probability in men and women from the UK","volume":"19","author":"Kanis","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_13","first-page":"602","article-title":"New technologies in the evaluation of bone fragility and its application in Endocrinology","volume":"67","author":"Alhambra","year":"2020","journal-title":"Endocrinol. Diabetes Nutr. (Engl. Ed.)"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/jbm4.10030","article-title":"Age-Related Deterioration of Bone Toughness Is Related to Diminishing Amount of Matrix Glycosaminoglycans (Gags)","volume":"2","author":"Wang","year":"2018","journal-title":"JBMR Plus"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.matbio.2020.09.002","article-title":"Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix","volume":"94","author":"Hua","year":"2020","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan form and function: A comprehensive nomenclature of proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_17","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (1999). Chapter 11: Proteoglycans and Glycosaminoglycans. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41592-018-0086-z","article-title":"The GAGOme: A cell-based library of displayed glycosaminoglycans","volume":"15","author":"Chen","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a005199","DOI":"10.1101\/cshperspect.a005199","article-title":"Golgi glycosylation","volume":"3","author":"Stanley","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bio060239","DOI":"10.1242\/bio.060239","article-title":"Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro","volume":"13","author":"Jalava","year":"2024","journal-title":"Biol. Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Huang, Y.F., Mizumoto, S., and Fujita, M. (2021). Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.709018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1146\/annurev.biochem.72.121801.161809","article-title":"A Genetic Approach to Mammalian Glycan Function","volume":"72","author":"Lowe","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1038\/s41467-023-42236-z","article-title":"Molecular mechanism of decision-making in glycosaminoglycan biosynthesis","volume":"14","author":"Sammon","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.sbi.2003.08.002","article-title":"Sulfotransferases in glycosaminoglycan biosynthesis","volume":"13","year":"2003","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/mrc.2168","article-title":"Towards a model of the mineral-organic interface in bone: NMR of the structure of synthetic glycosaminoglycan- and polyaspartate-calcium phosphate composites","volume":"46","author":"Best","year":"2008","journal-title":"Magn. Reson. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/BF00301609","article-title":"EDTA-insoluble, calcium-binding proteoglycan in bovine bone","volume":"56","author":"Hashimoto","year":"1995","journal-title":"Calcif. Tissue Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30504","DOI":"10.1074\/jbc.M004846200","article-title":"Bone morphogenetic protein-1 processes probiglycan","volume":"275","author":"Scott","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100207","DOI":"10.1016\/j.bonr.2019.100207","article-title":"Bone morphogenetic proteins: Their role in regulating osteoclast differentiation","volume":"10","author":"Huntley","year":"2019","journal-title":"Bone Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.bbrc.2009.12.067","article-title":"Decorin is processed by three isoforms of bone morphogenetic protein-1 (BMP1)","volume":"391","author":"Fisher","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.pmbts.2017.05.001","article-title":"Chapter Six-Matrix Metalloproteinases in Bone Resorption, Remodeling, and Repair","volume":"Volume 148","author":"Khalil","year":"2017","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.gep.2015.04.004","article-title":"MMP and TIMP temporal gene expression during osteocytogenesis","volume":"18","author":"Prideaux","year":"2015","journal-title":"Gene Expr. Patterns"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1021\/acsabm.9b01227","article-title":"IDG-SW3 Osteocyte Differentiation and Bone Extracellular Matrix Deposition Are Enhanced in a 3D Matrix Metalloproteinase-Sensitive Hydrogel","volume":"3","author":"Aziz","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1755-1536-6-9","article-title":"Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases","volume":"6","author":"Genovese","year":"2013","journal-title":"Fibrogenesis Tissue Repair."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.joca.2022.02.622","article-title":"Forward and reverse degradomics defines the proteolytic landscape of human knee osteoarthritic cartilage and the role of the serine protease HtrA1","volume":"30","author":"Bhutada","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.joca.2006.05.014","article-title":"The cleavage of biglycan by aggrecanases","volume":"14","author":"Melching","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R26","DOI":"10.1186\/ar1873","article-title":"Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: Identification of a new biglycan cleavage site","volume":"8","author":"Monfort","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41413-023-00303-7","article-title":"Aging impairs the osteocytic regulation of collagen integrity and bone quality","volume":"12","author":"Schurman","year":"2024","journal-title":"Bone Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Daquinag, A.C., Gao, Z., Fussell, C., Sun, K., and Kolonin, M.G. (2020). Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly. Cells, 9.","DOI":"10.3390\/cells9122646"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1016\/j.bbadis.2011.08.009","article-title":"Proteoglycan degradation by the ADAMTS family of proteinases","volume":"1812","author":"Stanton","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3109\/10409239509083490","article-title":"Enzymatic degradation of glycosaminoglycans","volume":"30","author":"Ernst","year":"1995","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3109\/03008209809028897","article-title":"The Modification of Alveolar Bone Proteoglycans by Reactive Oxygen Species In Vitro","volume":"37","author":"Moseley","year":"1998","journal-title":"Connect. Tissue Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0304-4165(95)00010-9","article-title":"The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro","volume":"1244","author":"Moseley","year":"1995","journal-title":"Biochim. Biophys. Acta (BBA)-General. Subj."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1089\/ars.2013.5634","article-title":"Glycosaminoglycan Degradation by Selected Reactive Oxygen Species","volume":"21","author":"Fuchs","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1042\/bj3220809","article-title":"Degradation of decorin by matrix metalloproteinases: Identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release","volume":"322","author":"Imai","year":"1997","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1111\/febs.12198","article-title":"Functional interactions between matrix metalloproteinases and glycosaminoglycans","volume":"280","author":"Tocchi","year":"2013","journal-title":"FEBS J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70011","DOI":"10.1002\/pgr2.70011","article-title":"Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling","volume":"2","author":"Kemberi","year":"2024","journal-title":"Proteoglycan Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/8756-3282(93)90235-3","article-title":"Increased intracortical remodeling following fatigue damage","volume":"14","author":"Mori","year":"1993","journal-title":"Bone"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s00223-011-9568-z","article-title":"Microcracks and Osteoclast Resorption Activity In Vitro","volume":"90","author":"Rumpler","year":"2012","journal-title":"Calcif. Tissue Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0021-9290(97)00029-8","article-title":"Crack growth resistance in cortical bone: Concept of microcrack toughening","volume":"30","author":"Vashishth","year":"1997","journal-title":"J. Biomech."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.orthres.2004.08.005","article-title":"The effect of bone microstructure on the initiation and growth of microcracks","volume":"23","author":"Taylor","year":"2005","journal-title":"J. Orthop. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bone.2007.10.009","article-title":"A unified theory for osteonal and hemi-osteonal remodeling","volume":"42","author":"Ruimerman","year":"2008","journal-title":"Bone"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1111\/febs.12214","article-title":"Biological functions of iduronic acid in chondroitin\/dermatan sulfate","volume":"280","author":"Thelin","year":"2013","journal-title":"FEBS J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shiflett, L.A., Tiede-Lewis, L.M., Xie, Y., Lu, Y., Ray, E.C., and Dallas, S.L. (2019). Collagen Dynamics During the Process of Osteocyte Embedding and Mineralization. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00178"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.22203\/eCM.v006a02","article-title":"Differential roles for small leucine-rich proteoglycans in bone formation","volume":"6","author":"Waddington","year":"2003","journal-title":"Eur. Cell Mater."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"120738","DOI":"10.1016\/j.carbpol.2023.120738","article-title":"A seminal perspective on the role of chondroitin sulfate in biomineralization","volume":"310","author":"Hao","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1101\/gad.1276205","article-title":"Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone","volume":"19","author":"Murshed","year":"2005","journal-title":"Genes Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"0108021","DOI":"10.1115\/1.4029176","article-title":"Biomechanics and mechanobiology of trabecular bone: A review","volume":"137","author":"Oftadeh","year":"2015","journal-title":"J. Biomech. Eng."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bone.2009.05.025","article-title":"The degree and distribution of cortical bone mineralization in the human femoral shaft change with age and sex in a microradiographic study","volume":"45","author":"Bergot","year":"2009","journal-title":"Bone"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00223-011-9497-x","article-title":"Measuring differences in compositional properties of bone tissue by confocal Raman spectroscopy","volume":"89","author":"Nyman","year":"2011","journal-title":"Calcif. Tissue Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00223-021-00825-4","article-title":"Measures of Bone Mineral Carbonate Content and Mineral Maturity\/Crystallinity for FT-IR and Raman Spectroscopic Imaging Differentially Relate to Physical\u2013Chemical Properties of Carbonate-Substituted Hydroxyapatite","volume":"109","author":"Taylor","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.bone.2006.06.026","article-title":"Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue","volume":"39","author":"Nyman","year":"2006","journal-title":"Bone"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"M110.006718","DOI":"10.1074\/mcp.M110.006718","article-title":"Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology","volume":"10","author":"Sroga","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bone.2011.04.009","article-title":"In situ accumulation of advanced glycation endproducts (AGEs) in bone matrix and its correlation with osteoclastic bone resorption","volume":"49","author":"Dong","year":"2011","journal-title":"Bone"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/jbmr.5650080902","article-title":"Distribution of noncollagenous proteins in the matrix of adult human bone: Evidence of anatomic and functional heterogeneity","volume":"8","author":"Ingram","year":"1993","journal-title":"J. Bone Miner. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1002\/jbmr.1927","article-title":"Architecture of the osteocyte network correlates with bone material quality","volume":"28","author":"Kerschnitzki","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"43638","DOI":"10.1074\/jbc.M202124200","article-title":"Age-related changes in human bone proteoglycan structure. Impact of osteogenesis imperfecta","volume":"277","author":"Grzesik","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jcp.1041510202","article-title":"Age-related changes in hyaluronan, proteoglycan, collagen, and osteonectin synthesis by human bone cells","volume":"151","author":"Fedarko","year":"1992","journal-title":"J. Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1042\/bj2950421","article-title":"Non-proteoglycan forms of biglycan increase with age in human articular cartilage","volume":"295","author":"Roughley","year":"1993","journal-title":"Biochem. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"116478","DOI":"10.1016\/j.bone.2022.116478","article-title":"Treatment of postmenopausal osteoporosis patients with teriparatide for 24 months reverts forming bone quality indices to premenopausal healthy control values","volume":"162","author":"Paschalis","year":"2022","journal-title":"Bone"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pei, S., Wang, S., Martinez, J.R., Parajuli, A., Kirn-Safran, C.B., Farach-Carson, M.C., Lu, X.L., and Wang, L. (2022). Osteocytic Pericellular Matrix (PCM): Accelerated Degradation under In Vivo Loading and Unloading Conditions Using a Novel Imaging Approach. Genes, 13.","DOI":"10.3390\/genes13010072"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/jbmr.4516","article-title":"Prioritization of Genes Relevant to Bone Fragility Through the Unbiased Integration of Aging Mouse Bone Transcriptomics and Human GWAS Analyses","volume":"37","author":"Kaya","year":"2022","journal-title":"J. Bone Miner. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"117163","DOI":"10.1016\/j.bone.2024.117163","article-title":"Aging decreases osteocyte peri-lacunar-canalicular system turnover in female C57BL\/6JN mice","volume":"186","author":"Vahidi","year":"2024","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e13056","DOI":"10.1111\/acel.13056","article-title":"Decreased pericellular matrix production and selection for enhanced cell membrane repair may impair osteocyte responses to mechanical loading in the aging skeleton","volume":"19","author":"Hagan","year":"2020","journal-title":"Aging Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/ten.teb.2020.0322","article-title":"Osteon: Structure, Turnover, and Regeneration","volume":"28","author":"Chang","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/bj2920661","article-title":"Identification and characterization of glycanated and non-glycanated forms of biglycan and decorin in the human intervertebral disc","volume":"292","author":"Johnstone","year":"1993","journal-title":"Biochem. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1369\/0022155420937371","article-title":"Biglycan in the Skeleton","volume":"68","author":"Kram","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/03008207.2019.1669577","article-title":"Evidence of biglycan structure-function in bone homeostasis and aging","volume":"61","author":"Miguez","year":"2020","journal-title":"Connect. Tissue Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/ar2453","article-title":"Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues","volume":"10","author":"Melrose","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/agm2.12121","article-title":"Oxidative stress in elderly population: A prevention screening study","volume":"3","author":"Gorni","year":"2020","journal-title":"Aging Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27298","DOI":"10.1074\/jbc.M702811200","article-title":"Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting \u03b2-Catenin from T Cell Factor-to Forkhead Box O-mediated Transcription","volume":"282","author":"Almeida","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative stress, aging, and diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1681\/ASN.2014101047","article-title":"Uremic Toxicity of Advanced Glycation End Products in CKD","volume":"27","author":"Stinghen","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/j.1523-1755.2004.00868.x","article-title":"Low-molecular-weight AGEs are associated with GFR and anemia in patients with type 2 diabetes","volume":"66","author":"Thomas","year":"2004","journal-title":"Kidney Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/rheumatology\/keg324","article-title":"Advanced glycation end-products pentosidine and N\u03f5-carboxymethyllysine are elevated in serum of patients with osteoporosis","volume":"42","author":"Hein","year":"2003","journal-title":"Rheumatology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"28116","DOI":"10.1074\/jbc.273.43.28116","article-title":"Dermatan Sulfate Released after Injury Is a Potent Promoter of Fibroblast Growth Factor-2 Function","volume":"273","author":"Penc","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"42815","DOI":"10.1074\/jbc.M204959200","article-title":"Dermatan Sulfate Binds and Potentiates Activity of Keratinocyte Growth Factor (FGF-7)","volume":"277","author":"Trowbridge","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1172\/JCI23755","article-title":"The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages","volume":"115","author":"Schaefer","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s11914-017-0413-9","article-title":"Effects of Aging on Fracture Healing","volume":"15","author":"Clark","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/35015116","article-title":"Effects of mechanical forces on maintenance and adaptation of form in trabecular bone","volume":"405","author":"Huiskes","year":"2000","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5371\/hp.2021.33.2.53","article-title":"Factors Affecting Periprosthetic Bone Loss after Hip Arthroplasty","volume":"33","author":"Lee","year":"2021","journal-title":"Hip Pelvis"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S8756-3282(00)00236-2","article-title":"Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age","volume":"26","author":"Vashishth","year":"2000","journal-title":"Bone"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/ar.a.20146","article-title":"Sexual dimorphism and age dependence of osteocyte lacunar density for human vertebral cancellous bone","volume":"282A","author":"Vashishth","year":"2005","journal-title":"Anat. Rec. Part A Discov. Mol. Cell. Evol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/8756-3282(95)00444-0","article-title":"Osteocyte density changes in aging and osteoporosis","volume":"18","author":"Mullender","year":"1996","journal-title":"Bone"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bone.2019.07.028","article-title":"3D analysis of the osteonal and interstitial tissue in human radii cortical bone","volume":"127","author":"Gauthier","year":"2019","journal-title":"Bone"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"14655","DOI":"10.1038\/s41598-024-63645-0","article-title":"Spatial control of perilacunar canalicular remodeling during lactation","volume":"14","author":"Sieverts","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.actbio.2025.09.040","article-title":"Fluorescent mapping of osteocyte-driven bone formation at pre-osteocyte and mature osteocyte lacunae","volume":"207","author":"Ford","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_97","first-page":"201","article-title":"Mean skeletal age: Its calculation, and theoretical effects on skeletal tracer physiology and on the physical characteristics of bone","volume":"11","author":"Hattner","year":"1963","journal-title":"Henry Ford Hosp. Med. Bull."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1114\/1.1623488","article-title":"Age-related changes of noncalcified collagen in human cortical bone","volume":"31","author":"Wang","year":"2003","journal-title":"Ann. Biomed. Eng."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1016\/j.jbiomech.2016.06.009","article-title":"Prevalent role of porosity and osteonal area over mineralization heterogeneity in the fracture toughness of human cortical bone","volume":"49","author":"Granke","year":"2016","journal-title":"J. Biomech."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1520\/JFS15385J","article-title":"Microscopic age changes in the human occipital bone","volume":"40","author":"Cool","year":"1995","journal-title":"J. Forensic Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/BF02196201","article-title":"Haversian bone formation rates determined by a new method in a mastodon, and in human diabetes mellitus and osteoporosis","volume":"6","author":"Wu","year":"1970","journal-title":"Calcif. Tissue Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"282.e1","DOI":"10.1016\/j.forsciint.2016.02.053","article-title":"Variation in osteon histomorphometrics and their impact on age-at-death estimation in older individuals","volume":"262","author":"Goliath","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"ref_103","unstructured":"Nanci, A. (2008). Bone. Ten Cate\u2019s Oral Histology, Mosby Elsevier."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Jee, W. (1983). The Skeletal Tissues, Histology: Cell and Tissue Biology, Elsevier Science Ltd.","DOI":"10.1007\/978-1-349-06859-3_6"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1210\/jcem-67-4-741","article-title":"Bone Formation Rate in Older Normal Women: Concurrent Assessment with Bone Histomorphometry, Calcium Kinetics, and Biochemical Markers","volume":"67","author":"Eastell","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1359\/jbmr.1999.14.7.1203","article-title":"Age-related changes in bone turnover in men","volume":"14","author":"Fatayerji","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.bone.2013.04.003","article-title":"Age-related reference intervals for bone turnover markers from an Australian reference population","volume":"55","author":"Jenkins","year":"2013","journal-title":"Bone"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e93771","DOI":"10.1172\/jci.insight.93771","article-title":"Old age causes de novo intracortical bone remodeling and porosity in mice","volume":"2","author":"Piemontese","year":"2017","journal-title":"JCI Insight"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1177\/172460089000500202","article-title":"Tartrate-resistant acid phosphatase (TRAP) activity in serum: Potential use in assessing bone resorption in patients with multiple myeloma","volume":"5","author":"Monti","year":"1990","journal-title":"Int. J. Biol. Markers"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1002\/ajmg.a.37209","article-title":"A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes","volume":"167A","author":"Jones","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ajhg.2011.05.021","article-title":"Faulty initiation of proteoglycan synthesis causes cardiac and joint defects","volume":"89","author":"Baasanjav","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00439-015-1549-2","article-title":"Skeletal dysplasia in a consanguineous clan from the island of Nias\/Indonesia is caused by a novel mutation in B3GAT3","volume":"134","author":"Budde","year":"2015","journal-title":"Hum. Genet."},{"key":"ref_113","first-page":"1580","article-title":"Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-report of the second family with B3GAT3 mutation and expansion of the phenotype","volume":"164A","author":"Tan","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/gim.2017.109","article-title":"B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation","volume":"20","author":"Yauy","year":"2018","journal-title":"Genet. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12190","DOI":"10.1074\/jbc.M110.100941","article-title":"Impairment of embryonic cell division and glycosaminoglycan biosynthesis in glucuronyltransferase-I-deficient mice","volume":"285","author":"Izumikawa","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41525-024-00413-z","article-title":"Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome","volume":"9","author":"Meester","year":"2024","journal-title":"NPJ Genom. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/gim.2016.126","article-title":"Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections","volume":"19","author":"Meester","year":"2017","journal-title":"Genet. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41413-024-00380-2","article-title":"Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness","volume":"13","author":"Hua","year":"2025","journal-title":"Bone Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1086\/301726","article-title":"Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses","volume":"62","author":"Wuyts","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bone.2004.09.025","article-title":"EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development","volume":"36","author":"Hilton","year":"2005","journal-title":"Bone"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ejhg.2014.60","article-title":"Expanding the clinical spectrum of B4GALT7 deficiency: Homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome","volume":"23","author":"Cartault","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.ajhg.2009.10.001","article-title":"Identification of CANT1 Mutations in Desbuquois Dysplasia","volume":"85","author":"Huber","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ajhg.2014.01.020","article-title":"XYLT1 mutations in Desbuquois dysplasia type 2","volume":"94","author":"Bui","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/jmedgenet-2020-107623","article-title":"Clinical and molecular features of 66 patients with musculocontractural Ehlers\u2212Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)","volume":"59","author":"Minatogawa","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1242\/dev.01948","article-title":"Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis","volume":"132","author":"Wight","year":"2005","journal-title":"Development"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e1197","DOI":"10.1002\/mgg3.1197","article-title":"Delineation of musculocontractural Ehlers-Danlos Syndrome caused by dermatan sulfate epimerase deficiency","volume":"8","author":"Lautrup","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/bdra.23300","article-title":"Dermatan sulfate epimerase 1 deficient mice as a model for human abdominal wall defects","volume":"100","author":"Gustafsson","year":"2014","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Shimbo, M., Suzuki, R., Fuseya, S., Sato, T., Kiyohara, K., Hagiwara, K., Okada, R., Wakui, H., Tsunakawa, Y., and Watanabe, H. (2017). Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0190333"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1210\/en.2008-0877","article-title":"Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression","volume":"150","author":"Ichikawa","year":"2009","journal-title":"Endocrinology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1210\/en.2014-1199","article-title":"Genetic rescue of glycosylation-deficient Fgf23 in the Galnt3 knockout mouse","volume":"155","author":"Ichikawa","year":"2014","journal-title":"Endocrinology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1038\/srep03701","article-title":"Chondroitin sulfate is indispensable for pluripotency and differentiation of mouse embryonic stem cells","volume":"4","author":"Izumikawa","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Job, F., Mizumoto, S., Smith, L., Couser, N., Brazil, A., Saal, H., Patterson, M., Gibson, M.I., Soden, S., and Miller, N. (2016). Functional validation of novel compound heterozygous variants in B3GAT3 resulting in severe osteopenia and fractures: Expanding the disease phenotype. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0344-9"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.matbio.2013.12.004","article-title":"Biglycan modulates angiogenesis and bone formation during fracture healing","volume":"35","author":"Berendsen","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_134","unstructured":"Courtney, T.H. (2005). Mechanical Behavior of Materials, Waveland Press. [2nd ed.]."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"116751","DOI":"10.1016\/j.bone.2023.116751","article-title":"Assessment of glycosaminoglycan content in bone using Raman spectroscopy","volume":"171","author":"Heath","year":"2023","journal-title":"Bone"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/03008209509016977","article-title":"The effect of glycosylaminoglycans on the mineralization of sheep periodontal ligament in vitro","volume":"33","author":"Kirkham","year":"1995","journal-title":"Connect. Tissue Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"106403","DOI":"10.1016\/j.jmbbm.2024.106403","article-title":"In-silico simulation of nanoindentation on bone using a 2D cohesive finite element model","volume":"151","author":"Xiao","year":"2024","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"104766","DOI":"10.1016\/j.jmbbm.2021.104766","article-title":"Removal of glycosaminoglycans affects the in situ mechanical behavior of extrafibrillar matrix in bone","volume":"123","author":"Han","year":"2021","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"110796","DOI":"10.1016\/j.jbiomech.2021.110796","article-title":"Contribution of glycosaminoglycans to the structural and mechanical properties of tendons\u2013A multiscale study","volume":"128","author":"Kirk","year":"2021","journal-title":"J. Biomech."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e4508","DOI":"10.1002\/pro.4508","article-title":"Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native extracellular matrix environment","volume":"32","author":"Roth","year":"2023","journal-title":"Protein Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1152\/japplphysiol.90748.2008","article-title":"Contribution of glycosaminoglycans to viscoelastic tensile behavior of human ligament","volume":"106","author":"Lujan","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"7589","DOI":"10.1113\/JP286609","article-title":"Glycosaminoglycans influence regional mechanics in young but not old Achilles tendons","volume":"603","author":"Blank","year":"2025","journal-title":"J. Physiol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"24160","DOI":"10.1074\/jbc.M116.751974","article-title":"Heparan Sulfate Regulates the Structure and Function of Osteoprotegerin in Osteoclastogenesis","volume":"291","author":"Li","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"17187","DOI":"10.1073\/pnas.2005859117","article-title":"Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site","volume":"117","author":"Li","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"20510","DOI":"10.1038\/s41598-020-77510-3","article-title":"The heparan sulfate proteoglycan Syndecan-1 influences local bone cell communication via the RANKL\/OPG axis","volume":"10","author":"Timmen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/S0006-291X(03)01500-6","article-title":"Heparan sulfate is required for bone morphogenetic protein-7 signaling","volume":"308","author":"Irie","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Diehl, V., Huber, L.S., Trebicka, J., Wygrecka, M., Iozzo, R.V., and Schaefer, L. (2021). The Role of Decorin and Biglycan Signaling in Tumorigenesis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.801801"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Giatagana, E.-M., Berdiaki, A., Gaardl\u00f8s, M., Samsonov, S.A., Tzanakakis, G.N., and Nikitovic, D. (2022). Biglycan Interacts with Type I Insulin-like Receptor (IGF-IR) Signaling Pathway to Regulate Osteosarcoma Cell Growth and Response to Chemotherapy. Cancers, 14.","DOI":"10.3390\/cancers14051196"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"15846","DOI":"10.1038\/s41598-019-52358-4","article-title":"Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13\/ADAMTS5 production in chondrocytes","volume":"9","author":"Jung","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Goodall, K.J., Poon, I.K., Phipps, S., and Hulett, M.D. (2014). Soluble heparan sulfate fragments generated by heparanase trigger the release of pro-inflammatory cytokines through TLR-4. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109596"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1096\/fj.05-4682rev","article-title":"Glycosaminoglycans and their proteoglycans: Host-associated molecular patterns for initiation and modulation of inflammation","volume":"20","author":"Taylor","year":"2006","journal-title":"FASEB J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"eadq8545","DOI":"10.1126\/sciadv.adq8545","article-title":"Biglycan fragment modulates TGF-\u03b2 activity in intervertebral disc via an eIF6-coupled intracellular path","volume":"11","author":"Zhu","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1016\/j.joca.2022.07.005","article-title":"Biglycan neo-epitope (BGN262), a novel biomarker for screening early changes in equine osteoarthritic subchondral bone","volume":"30","author":"Adepu","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1074\/jbc.274.8.4489","article-title":"Decorin is a biological ligand for the epidermal growth factor receptor","volume":"274","author":"Iozzo","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1002\/jbmr.2105","article-title":"Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system","volume":"29","author":"Wang","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"18087","DOI":"10.1073\/pnas.0404504102","article-title":"Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair","volume":"101","author":"Venkatesan","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.matbio.2018.02.025","article-title":"Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration","volume":"71\u201372","author":"Silagi","year":"2018","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s00223-008-9138-1","article-title":"Osteoadherin is upregulated by mature osteoblasts and enhances their in vitro differentiation and mineralization","volume":"82","author":"Rehn","year":"2008","journal-title":"Calcif. Tissue Int."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bone.2012.09.016","article-title":"Effects of PTH on osteocyte function","volume":"54","author":"Bellido","year":"2013","journal-title":"Bone"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jbm4.10021","article-title":"Parathyroid Hormone Signaling in Osteocytes","volume":"2","author":"Wein","year":"2018","journal-title":"JBMR Plus"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11914-019-00555-5","article-title":"Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation","volume":"17","author":"Liu","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1002\/mrm.24870","article-title":"Validation of quantitative bound- and pore-water imaging in cortical bone","volume":"71","author":"Manhard","year":"2014","journal-title":"Magn. Reson. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/jbmr.1535","article-title":"Quantitative ultrashort echo time (UTE) MRI of human cortical bone: Correlation with porosity and biomechanical properties","volume":"27","author":"Bae","year":"2012","journal-title":"J. Bone Miner. Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/4\/572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:16:46Z","timestamp":1776226606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/4\/572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":163,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["biom16040572"],"URL":"https:\/\/doi.org\/10.3390\/biom16040572","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]}}}