{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:22:08Z","timestamp":1774610528871,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES","award":["LA\/P\/0008\/2020"],"award-info":[{"award-number":["LA\/P\/0008\/2020"]}]},{"name":"FCT\/MCTES","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"FCT\/MCTES","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Diabetes mellitus is a widespread metabolic disorder linked to numerous systemic complications, including adverse effects on skeletal health, such as increased bone fragility and fracture risk. Emerging evidence suggests that high glucose may disrupt the extracellular matrix (ECM) of bone, potentially altering its composition and organization. Collagen, the primary organic component of the ECM, is critical for maintaining structural integrity and biomechanical properties. However, definitive evidence and a comprehensive understanding of the molecular mechanisms through which high glucose impacts the ECM and collagen remain elusive. This study employed an ex vivo embryonic chicken femur model to investigate the effects of high glucose on the collagenous matrix. A comprehensive approach integrating histological evaluation, histomorphometry, ATR-FTIR spectroscopy, and proteomics was adopted to unravel structural, biochemical, and molecular changes in the ECM. Histomorphometric analysis revealed disrupted collagen fibril architecture, characterized by altered fibril diameter, alignment, and spatial organization. ATR-FTIR spectroscopy highlighted biochemical modifications, including non-enzymatic glycation that impaired collagen crosslinking and reduced matrix integrity. Proteomic profiling unveiled significant alterations in ECM composition and function, including downregulation of key collagen crosslinking enzymes and upregulation of inflammatory and coagulation pathways. High glucose profoundly disrupts the collagenous matrix of bone, weakening its structural integrity and organization. These findings emphasize the critical impact of high glucose environments on extracellular matrix composition and bone quality, offering insights into the mechanisms behind diabetic bone fragility and guiding future research toward targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells14020130","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T10:27:58Z","timestamp":1737109678000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of High Glucose on Bone Collagenous Matrix Composition, Structure, and Organization: An Integrative Analysis Using an Ex Vivo Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6451-9990","authenticated-orcid":false,"given":"Rita","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"Endocrine and Metabolic Research, UMIB Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2073-7643","authenticated-orcid":false,"given":"Ricardo N. M. J.","family":"P\u00e1scoa","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Raquel","family":"Bernardino","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Research, UMIB Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-2123","authenticated-orcid":false,"given":"Pedro S.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lin, X., Patil, S., Gao, Y.G., and Qian, A. (2020). The Bone Extracellular Matrix in Bone Formation and Regeneration. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00757"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alcorta-Sevillano, N., Mac\u00edas, I., Infante, A., and Rodr\u00edguez, C.I. (2020). Deciphering the Relevance of Bone ECM Signaling. Cells, 9.","DOI":"10.3390\/cells9122630"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s11914-014-0213-4","article-title":"Biological regulation of bone quality","volume":"12","author":"Alliston","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_4","first-page":"S51","article-title":"Biochemical and biophysical aspects of collagen nanostructure in the extracellular matrix","volume":"56","author":"Varga","year":"2007","journal-title":"Physiol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bansode, S., Bashtanova, U., Li, R., Clark, J., M\u00fcller, K.H., Puszkarska, A., Goldberga, I., Chetwood, H.H., Reid, D.G., and Colwell, L.J. (2020). Glycation changes molecular organization and charge distribution in type I collagen fibrils. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-60250-9"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Arseni, L., Lombardi, A., and Orioli, D. (2018). From Structure to Phenotype: Impact of Collagen Alterations on Human Health. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051407"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/jcb.20605","article-title":"Diverse biological functions of extracellular collagen processing enzymes","volume":"96","author":"Trackman","year":"2005","journal-title":"J. Cell Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rieppo, L., Janssen, L., Rahunen, K., Lehenkari, P., Finnil\u00e4, M.A.J., and Saarakkala, S. (2019). Histochemical quantification of collagen content in articular cartilage. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224839"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Argyropoulos, A.J., Robichaud, P., Balimunkwe, R.M., Fisher, G.J., Hammerberg, C., Yan, Y., and Quan, T. (2016). Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153806"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116569","DOI":"10.1016\/j.bone.2022.116569","article-title":"Advanced glycation end products and bone\u2014How do we measure them and how do they correlate with bone mineral density and fractures? A systematic review and evaluation of precision of measures","volume":"165","author":"Brandt","year":"2022","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Delle Monache, S., Pulcini, F., Frosini, R., Mattei, V., Talesa, V.N., and Antognelli, C. (2021). Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2\/Glo1 Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10050716"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1111\/jdi.13528","article-title":"Glyoxal-induced formation of advanced glycation end-products in type 1 collagen decreases both its strength and flexibility in vitro","volume":"12","author":"Kitamura","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s11914-014-0202-7","article-title":"Diabetes, Collagen, and Bone Quality","volume":"12","author":"Saito","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s11914-019-00538-6","article-title":"Effects of Diabetes on Bone Material Properties","volume":"17","author":"Lekkala","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bone.2018.10.024","article-title":"Bone collagen network integrity and transverse fracture toughness of human cortical bone","volume":"120","author":"Willett","year":"2019","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/nyas.13572","article-title":"Bone quality changes associated with aging and disease: A review","volume":"1410","author":"Boskey","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.febslet.2007.03.063","article-title":"Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling","volume":"581","author":"Hamamura","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/jor.21538","article-title":"Age-related changes in organization and content of the collagen matrix in rabbit cortical bone","volume":"30","author":"Turunen","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1753-0407.2009.00049.x","article-title":"Diabetes and skeletal health","volume":"1","author":"Yaturu","year":"2009","journal-title":"J. Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s12551-017-0315-1","article-title":"Biophysical aspects of biomineralization","volume":"9","author":"Bolean","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116355","DOI":"10.1016\/j.bone.2022.116355","article-title":"A new ex vivo model of the bone tissue response to the hyperglycemic environment\u2014The embryonic chicken femur organotypic culture in high glucose conditions","volume":"158","author":"Martin","year":"2022","journal-title":"Bone"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.22203\/eCM.v026a07","article-title":"A new take on an old story: Chick limb organ culture for skeletal niche development and regenerative medicine evaluation","volume":"26","author":"Smith","year":"2013","journal-title":"Eur. Cells Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116672","DOI":"10.1016\/j.bone.2023.116672","article-title":"Longitudinal alterations in bone morphometry, mechanical integrity and composition in Type-2 diabetes in a Zucker diabetic fatty (ZDF) rat","volume":"170","author":"Monahan","year":"2023","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.joen.2021.06.006","article-title":"The Osteogenic Assessment of Mineral Trioxide Aggregate\u2013based Endodontic Sealers in an Organotypic Ex Vivo Bone Development Model","volume":"47","author":"Gomes","year":"2021","journal-title":"J. Endod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1109\/TSMC.1979.4310076","article-title":"A Threshold Selection Method from Gray-Level Histograms","volume":"9","author":"Otsu","year":"1979","journal-title":"IEEE Trans. Syst. Man Cybern."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF01002772","article-title":"Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections","volume":"11","author":"Junqueira","year":"1979","journal-title":"Histochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1161\/STROKEAHA.108.528091","article-title":"Effect of Aging on Elastin Functionality in Human Cerebral Arteries","volume":"40","author":"Fonck","year":"2009","journal-title":"Stroke"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/cem.785","article-title":"Partial least squares for discrimination","volume":"17","author":"Barker","year":"2003","journal-title":"J. Chemom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.compag.2016.05.014","article-title":"Exploratory study on vineyards soil mapping by visible\/near-infrared spectroscopy of grapevine leaves","volume":"127","author":"Lopo","year":"2016","journal-title":"Comput. Electron. Agric."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1007\/s00198-017-4019-y","article-title":"Vibrational spectroscopic techniques to assess bone quality","volume":"28","author":"Paschalis","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Os\u00f3rio, H., Silva, C., Ferreira, M., Gullo, I., M\u00e1ximo, V., Barros, R., Mendon\u00e7a, F., Oliveira, C., and Carneiro, F. (2021). Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030407"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12018-018-9255-y","article-title":"Fourier Transform Infrared Spectroscopy of Bone Tissue: Bone Quality Assessment in Preclinical and Clinical Applications of Osteoporosis and Fragility Fracture","volume":"17","author":"Kourkoumelis","year":"2019","journal-title":"Clin. Rev. Bone Miner. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/05704928.2018.1431923","article-title":"Fourier transform infrared spectroscopy (FTIR) application chemical characterization of enamel, dentin and bone","volume":"53","author":"Lopes","year":"2018","journal-title":"Appl. Spectrosc. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.micron.2010.09.010","article-title":"Collagen type I amide I band infrared spectroscopy","volume":"42","author":"Mello","year":"2011","journal-title":"Micron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ab.2005.10.009","article-title":"Infrared spectroscopy used to evaluate glycosylation of proteins","volume":"348","author":"Khajehpour","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Donat, A., Knapstein, P.-R., Jiang, S., Baranowsky, A., Ballhause, T.-M., Frosch, K.-H., and Keller, J. (2021). Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084120"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nrneph.2011.149","article-title":"Cellular and molecular mechanisms of renal fibrosis","volume":"7","author":"Liu","year":"2011","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.exer.2014.08.011","article-title":"Extracellular matrix, gap junctions, and retinal vascular homeostasis in diabetic retinopathy","volume":"133","author":"Roy","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_39","first-page":"2469","article-title":"Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head","volume":"10","author":"Yang","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bian, H., Zhu, T., Liang, Y., Hei, R., Zhang, X., Li, X., Chen, J., Lu, Y., Gu, J., and Qiao, L. (2021). Expression Profiling and Functional Analysis of Candidate Col10a1 Regulators Identified by the TRAP Program. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.683939"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Carvalho, M.S., Cabral, J.M.S., da Silva, C.L., and Vashishth, D. (2021). Bone Matrix Non-Collagenous Proteins in Tissue Engineering: Creating New Bone by Mimicking the Extracellular Matrix. Polymers, 13.","DOI":"10.3390\/polym13071095"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/jcb.1115","article-title":"Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development","volume":"82","author":"Gori","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"239","DOI":"10.7150\/ijbs.29063","article-title":"Clopidogrel Reduces Fibronectin Accumulation and Improves Diabetes-Induced Renal Fibrosis","volume":"15","author":"Zheng","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s11239-021-02456-w","article-title":"Blood coagulation factor X: Molecular biology, inherited disease, and engineered therapeutics","volume":"52","author":"Camire","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dhar, A., Sadiq, F., Anstee, Q.M., Levene, A.P., Goldin, R.D., and Thursz, M.R. (2018). Thrombin and factor Xa link the coagulation system with liver fibrosis. BMC Gastroenterol., 18.","DOI":"10.1186\/s12876-018-0789-8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-\u03b2: The master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Motta, G., Juliano, L., and Chagas, J.R. (2023). Human plasma kallikrein: Roles in coagulation, fibrinolysis, inflammation pathways, and beyond. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1188816"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"534291","DOI":"10.1155\/2012\/534291","article-title":"Complement activation and inhibition in wound healing","volume":"2012","author":"Cazander","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.joca.2008.09.004","article-title":"Changes in spatial collagen content and collagen network architecture in porcine articular cartilage during growth and maturation","volume":"17","author":"Rieppo","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Unal, M., Uppuganti, S., Leverant, C.J., Creecy, A., Granke, M., Voziyan, P., and Nyman, J.S. (2018). Assessing glycation-mediated changes in human cortical bone with Raman spectroscopy. J. Biophotonics, 11.","DOI":"10.1002\/jbio.201700352"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bone.2017.01.015","article-title":"Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging","volume":"97","author":"Schmidt","year":"2017","journal-title":"Bone"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bone.2015.03.010","article-title":"Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study","volume":"76","author":"Mieczkowska","year":"2015","journal-title":"Bone"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s00223-015-9985-5","article-title":"Effects of Collagen Crosslinking on Bone Material Properties in Health and Disease","volume":"97","author":"Saito","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1359\/jbmr.2001.16.10.1821","article-title":"Spectroscopic Characterization of Collagen Cross-Links in Bone","volume":"16","author":"Paschalis","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/s11914-016-0332-1","article-title":"Advanced Glycation End Products, Diabetes, and Bone Strength","volume":"14","author":"Yamamoto","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Izu, Y., and Birk, D.E. (2023). Collagen XII mediated cellular and extracellular mechanisms in development, regeneration, and disease. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1129000"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.3346\/jkms.2021.36.e239","article-title":"Effects of Advanced Glycation End Products on Differentiation and Function of Osteoblasts and Osteoclasts","volume":"36","author":"Park","year":"2021","journal-title":"J. Korean Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e10212","DOI":"10.1002\/jbm4.10212","article-title":"Impaired Gastric Hormone Regulation of Osteoblasts and Lysyl Oxidase Drives Bone Disease in Diabetes Mellitus","volume":"3","author":"Daley","year":"2019","journal-title":"JBMR Plus"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.matbio.2016.01.001","article-title":"Enzymatic and non-enzymatic functions of the lysyl oxidase family in bone","volume":"52\u201354","author":"Trackman","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12697","DOI":"10.1074\/jbc.RA120.014504","article-title":"Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix","volume":"295","author":"Bathish","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.chemolab.2003.12.010","article-title":"A User-Friendly Guide to Multivariate Calibration and Classificationtion, T. N\u00e6s, T. Isaksson, T. Fearn, T. Davies: Chichester: NIR Publications","volume":"71","author":"Phatak","year":"2004","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Limirio, P.H.J.O., da Rocha Junior, H.A., Morais, R.B.d., Hiraki, K.R.N., Balbi, A.P.C., Soares, P.B.F., and Dechichi, P. (2018). Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191694"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2271","DOI":"10.1210\/clinem\/dgab027","article-title":"Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes","volume":"106","author":"Sihota","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/130\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:30:28Z","timestamp":1759919428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14020130"],"URL":"https:\/\/doi.org\/10.3390\/cells14020130","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]}}}