{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:00:45Z","timestamp":1790949645699,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzymeN-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (n=6) and from untreated (n=8) and ERT-treated (n=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified\/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.<\/jats:p>","DOI":"10.3390\/ijms22116165","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"6165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Plasma Proteomic Analysis in Morquio A Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-1341","authenticated-orcid":false,"given":"Jos\u00e9 V.","family":"\u00c1lvarez","sequence":"first","affiliation":[{"name":"Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"},{"name":"Skeletal Dysplasia Lab Nemours Biomedical Research Nemours\/Alfred I, duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-3079","authenticated-orcid":false,"given":"Susana B.","family":"Bravo","sequence":"additional","affiliation":[{"name":"Proteomic Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednicoUniversitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Pilar","family":"Chantada-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Proteomic Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednicoUniversitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda","family":"Barbosa-Gouveia","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-2812","authenticated-orcid":false,"given":"Crist\u00f3bal","family":"Col\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olalla","family":"L\u00f3pez-Suarez","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Skeletal Dysplasia Lab Nemours Biomedical Research Nemours\/Alfred I, duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-2253","authenticated-orcid":false,"given":"Francisco J.","family":"Otero-Espinar","sequence":"additional","affiliation":[{"name":"Paraquasil Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, 15872 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-9905","authenticated-orcid":false,"given":"Mar\u00eda L.","family":"Couce","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0006-291X(74)91022-5","article-title":"Morquio\u2019s syndrome: Deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase","volume":"61","author":"Matalon","year":"1974","journal-title":"Biochem. Biophys Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1172\/JCI108345","article-title":"N-acetylgalactosamine-6-sulfate sulfatase in man. Absence of the enzyme in Morquio disease","volume":"57","author":"Singh","year":"1976","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1126\/science.199.4324.79","article-title":"Deficiencies of glucosamine-6-sulfate or galactosamine-6-sulfate sulfatases are responsible for different mucopolysaccharidoses","volume":"199","author":"Ginsberg","year":"1978","journal-title":"Science"},{"key":"ref_4","first-page":"141","article-title":"Morquio A syndrome: Diagnosis and current and future therapies","volume":"12","author":"Tomatsu","year":"2014","journal-title":"Pediatr. Endocrinol. Rev. PER"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ajmg.a.36833","article-title":"International Guidelines for the Management and Treatment of Morquio A Syndrome","volume":"167","author":"Hendriksz","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ymgme.2016.11.007","article-title":"Mucopolysaccharidosis IVA and glycosaminoglycans","volume":"120","author":"Khan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ymgme.2018.05.004","article-title":"Diagnosis and prognosis of Mucopolysaccharidosis IVA","volume":"125","author":"Peracha","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2018.03.004","article-title":"Growth impairment in mucopolysaccharidoses","volume":"124","author":"Melbouci","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2174\/138920111795542615","article-title":"Mucopolysaccharidosis type IVA (Morquio A disease): Clinical review and current treatment","volume":"12","author":"Tomatsu","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_10","first-page":"59","article-title":"Mortality in patients with Morquio syndrome A","volume":"15","author":"Lavery","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ymgme.2018.02.011","article-title":"Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfasealfa enzyme replacement therapy (MOR-002\/MOR-100), representing 5 years of treatment","volume":"123","author":"Hendriksz","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1080\/17512433.2017.1260000","article-title":"Elosulfasealfa (BMN 110) for the treatment of mucopolysaccharidosis IVA (Morquio A Syndrome)","volume":"9","author":"Hendriksz","year":"2016","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13023-019-1074-9","article-title":"Recommendations for the management of MPS IVA: Systematic evidence- and consensus-based guidance","volume":"14","author":"Akyol","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1517\/21678707.2015.1086640","article-title":"Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): Effect and limitations","volume":"3","author":"Tomatsu","year":"2015","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/mt.2010.32","article-title":"Enhancement of drug delivery: Enzyme-replacement therapy for murine Morquio A syndrome","volume":"18","author":"Tomatsu","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s40265-019-01147-4","article-title":"Therapeutic Options for Mucopolysaccharidoses: Current and Emerging Treatments","volume":"79","author":"Sawamoto","year":"2019","journal-title":"Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.clinthera.2016.11.017","article-title":"Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study","volume":"39","author":"Long","year":"2017","journal-title":"Clin. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s10038-019-0604-6","article-title":"Effect of enzyme replacement therapy on the growth of patients with Morquio A","volume":"64","author":"Doherty","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymgme.2015.09.007","article-title":"Obstructive airway in Morquio A syndrome, the past, the present and the future","volume":"117","author":"Tomatsu","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.2147\/DDDT.S68562","article-title":"Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome","volume":"9","author":"Tomatsu","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s40262-014-0173-y","article-title":"Pharmacokinetic and Pharmacodynamic Evaluation of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients with Morquio A Syndrome","volume":"53","author":"Qi","year":"2014","journal-title":"Clin. Pharmacokinet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.joca.2007.04.008","article-title":"A molecular and histological characterization of cartilage from patients with Morquio syndrome","volume":"15","author":"Roseti","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","first-page":"100455","article-title":"Biomarkers in patients with mucopolysaccharidosis type II and IV","volume":"19","author":"Fujitsuka","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1700242","DOI":"10.1002\/pmic.201700242","article-title":"Label-Free Quantitative Phosphoproteomics Reveals Regulation of Vasodilator-Stimulated Phosphoprotein upon Stathmin-1 Silencing in a Pair of Isogenic Colorectal Cancer Cell Lines","volume":"18","author":"Tan","year":"2018","journal-title":"Proteomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.dib.2018.02.062","article-title":"A new SWATH ion library for mouse adult hippocampal neural stem cells","volume":"18","author":"Braccia","year":"2018","journal-title":"Data Brief"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1800164","DOI":"10.1002\/pmic.201800164","article-title":"Quantitative proteomics by SWATH-MS suggest an association between circulating exosomes and maternal metabolic changes in gestational diabetes mellitus","volume":"19","author":"Jayabalan","year":"2019","journal-title":"Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1021\/acs.jproteome.7b00505","article-title":"Multiplex and Label-Free Relative Quantification Approach for Studying Protein Abundance of Drug Metabolizing Enzymes in Human Liver Microsomes using SWATH-MS","volume":"16","author":"Jamwal","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Zhu, J., Lu, C., Zhang, Q., Xie, W., Sun, P., Dong, X., Yue, L., Sun, Y., and Yi, X. (2018). Identification of Protein Abundance Changes in Hepatocellular Carcinoma Tissues Using PCT\u2013SWATH. Proteom. Clin. Appl., 1\u201313.","DOI":"10.1002\/prca.201700179"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.21873\/cgp.20114","article-title":"A Comprehensive Proteome Analysis of Peripheral Blood Mononuclear Cells (PBMCs) to Identify Candidate Biomarkers of Pancreatic Cancer","volume":"16","author":"Li","year":"2019","journal-title":"Cancer Genom. Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuint.2015.04.004","article-title":"SWATH analysis of the synaptic proteome in Alzheimer\u2019s disease","volume":"87","author":"Chang","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/pmic.201300432","article-title":"Top-down proteomics in health and disease: Challenges and opportunities","volume":"14","author":"Gregorich","year":"2014","journal-title":"Proteomics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez, J.V., Bravo, S.B., Chantada-Vazquez, M.P., Col\u00f3n, C., De Castro, M.J., Morales, M., Vitoria, I., Tomatsu, S., Otero-Espinar, F.J., and Couce, M.L. (2020). Characterization of New Proteomic Biomarker Candidates in Mucopolysaccharidosis Type IVA. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010226"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1750-1172-6-84","article-title":"Biomarker analysis of Morquio syndrome: Identification of disease state and drug responsive markers","volume":"6","author":"Martell","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1530\/JOE-14-0440","article-title":"Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver","volume":"224","author":"Zhang","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_35","first-page":"1","article-title":"Di-sulfated Keratan Sulfate as a Novel Biomarker for Mucopolysaccharidosis II, IVA, and IVB","volume":"21","author":"Shimada","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/jmd2.12132","article-title":"Chondroitin sulfate disaccharide is a specific and sensitive biomarker for mucopolysaccharidosis type IVA","volume":"55","author":"Chin","year":"2020","journal-title":"JIMD Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez, J.V., Bravo, S.B., Garc\u00eda-Vence, M., De Castro, M.J., Luzardo, A., Col\u00f3n, C., Tomatsu, S., Otero-Espinar, F.J., and Couce, M.L. (2019). Proteomic Analysis in Morquio A Cells Treated with Immobilized Enzymatic Replacement Therapy on Nanostructured Lipid Systems. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184610"},{"key":"ref_38","first-page":"45","article-title":"Current and emerging management options for patients with Morquio A syndrome","volume":"9","author":"Algahim","year":"2013","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Eliyahu, E., Wolfson, T., Ge, Y., Jepsen, K.J., Schuchman, E.H., and Simonaro, C.M. (2011). Anti-TNF-Alpha Therapy Enhances the Effects of Enzyme Replacement Therapy in Rats with Mucopolysaccharidosis Type VI. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022447"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/cvr\/cvw075","article-title":"Extracellular matrix remodelling in response to venous hypertension: Proteomics of human varicose veins","volume":"110","author":"Oklu","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/S0021-9258(18)45872-3","article-title":"Binding of vitronectin-thrombin-antithrombin III complex to human endothelial cells is mediated by the heparin binding site of vitronectin","volume":"267","author":"Preissner","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1093\/nar\/gkg788","article-title":"The inflammation-induced down-regulation of plasma Fetuin-A (alpha2HS-Glycoprotein) in liver results from the loss of interaction between long C\/EBP isoforms at two neighbouring binding sites","volume":"31","author":"Gangneux","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00223-012-9690-6","article-title":"The role of fetuin-A in physiological and pathological mineralization","volume":"93","author":"Brylka","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1161\/CIRCRESAHA.110.234260","article-title":"Fetuin-A regulation of calcified matrix metabolism","volume":"108","author":"Heiss","year":"2011","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"625","DOI":"10.2174\/156652412800620039","article-title":"Anti-inflammatory role of Fetuin-A in Injury and Infection","volume":"12","author":"Wang","year":"2012","journal-title":"Curr. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1021\/acs.jproteome.6b01070","article-title":"Intra- and Interskeletal Proteome Variations in Fresh and Buried Bones","volume":"16","author":"Procopio","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1161\/01.ATV.14.9.1475","article-title":"Serum amyloid A protein family. Differential induction by oxidized lipids in mouse strains","volume":"14","author":"Liao","year":"1994","journal-title":"Arterioscler. Thromb. J. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.4049\/jimmunol.155.8.4004","article-title":"Serum amyloid A induces calcium mobilization and chemotaxis of human monocytes by activating a pertussis toxin-sensitive signaling pathway","volume":"155","author":"Badolato","year":"1995","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1161\/01.ATV.20.3.763","article-title":"Role of serum amyloid A during metabolism of acute-phase HDL by macrophages","volume":"20","author":"Artl","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.1074\/jbc.M405009200","article-title":"Serum amyloid A binding to CLA-1 (CD36 and LIMPII analogous-1) mediates serum amyloid A protein-induced activation of ERK1\/2 and p38 mitogen-activated protein kinases","volume":"280","author":"Baranova","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s10020-018-0047-0","article-title":"Serum amyloid\u2014A review","volume":"24","author":"Sack","year":"2018","journal-title":"Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00418-012-1062-9","article-title":"Retinol-binding protein 4 is expressed in chondrocytes of developing mouse long bones: Implications for a local role in formation of the secondary ossification center","volume":"139","author":"Hatfield","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bone.2018.02.018","article-title":"Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1\/2 signaling pathway","volume":"110","author":"Abdallah","year":"2018","journal-title":"Bone"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15953","DOI":"10.1021\/bi002189x","article-title":"Clusterin is an ATP-independent chaperone with very broad substrate specificity that stabilizes stressed proteins in a folding-competent state","volume":"39","author":"Poon","year":"2000","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39532","DOI":"10.1074\/jbc.M204855200","article-title":"Mildly Acidic pH Activates the Extracellular Molecular Chaperone Clusterin","volume":"277","author":"Poon","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1021\/bi062082v","article-title":"Effects of Glycosylation on the Structure and Function of the Extracellular Chaperone Clusterin","volume":"46","author":"Stewart","year":"2007","journal-title":"Biochemistry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1074\/jbc.M109.079566","article-title":"Identification of Human Plasma Proteins as Major Clients for the Extracellular Chaperone Clusterin","volume":"285","author":"Wyatt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.cca.2011.06.001","article-title":"Practical and reliable enzyme test for the detection of mucopolysaccharidosis IVA (Morquio Syndrome type A) in dried blood samples","volume":"412","author":"Camelier","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103581","DOI":"10.1016\/j.jprot.2019.103581","article-title":"Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers","volume":"212","author":"Vence","year":"2020","journal-title":"J. Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:51Z","timestamp":1760163111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116165"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116165","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]}}}