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To improve therapeutic approaches, identification of specific molecules\/biomarkers enabling early determination of this disease is needed. This study aimed at identifying, with the use of proteomics\/mass spectrometry, novel OA-specific serum biomarkers. As obesity is a major risk factor for OA, we discriminated obesity-regulated proteins to target only OA-specific proteins as biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum from the Osteoarthritis Initiative cohort was used and divided into 3 groups: controls (<jats:italic>n<\/jats:italic>=8), OA-obese (<jats:italic>n<\/jats:italic>=10) and OA-non-obese (<jats:italic>n<\/jats:italic>=10). Proteins were identified and quantified from the liquid chromatography\u2013tandem mass spectrometry analyses using MaxQuant software. Statistical analysis used the Limma test followed by the Benjamini-Hochberg method. To compare the proteomic profiles, the multivariate unsupervised principal component analysis (PCA) followed by the pairwise comparison was used. To select the most predictive\/discriminative features, the supervised linear classification model sparse partial least squares regression discriminant analysis (sPLS-DA) was employed. Validation of three differential proteins was performed with protein-specific assays using plasma from a cohort derived from the Newfoundland Osteoarthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 509 proteins were identified, and 279 proteins were quantified. PCA-pairwise differential comparisons between the 3 groups revealed that 8 proteins were differentially regulated between the OA-obese and\/or OA-non-obese with controls. Further experiments using the sPLS-DA revealed two components discriminating OA from controls (component 1, 9 proteins), and OA-obese from OA-non-obese (component 2, 23 proteins). Proteins from component 2 were considered related to obesity. In component 1, compared to controls, 7 proteins were significantly upregulated by both OA groups and 2 by the OA-obese. Among upregulated proteins from both OA groups, some of them alone would not be a suitable choice as specific OA biomarkers due to their rather non-specific role or their strong link to other pathological conditions. Altogether, data revealed that the protein CRTAC1 appears to be a strong OA biomarker candidate. Other potential new biomarker candidates are the proteins FBN1, VDBP, and possibly SERPINF1. Validation experiments revealed statistical differences between controls and OA for FBN1 (<jats:italic>p<\/jats:italic>=0.044) and VDPB (<jats:italic>p<\/jats:italic>=0.022), and a trend for SERPINF1 (<jats:italic>p<\/jats:italic>=0.064).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study suggests that 4 proteins, CRTAC1, FBN1, VDBP, and possibly SERPINF1, warrant further investigation as potential new biomarker candidates for the whole OA population.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13075-022-02801-1","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T07:03:24Z","timestamp":1653289404000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Mass spectrometry-based proteomics identify novel serum osteoarthritis biomarkers"],"prefix":"10.1186","volume":"24","author":[{"given":"Ginette","family":"Tardif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Par\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Gotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Roux-Dalvai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Droit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangju","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Fahmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-383X","authenticated-orcid":false,"given":"Johanne","family":"Martel-Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"2801_CR1","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1002\/art.1780300811","volume":"30","author":"DT Felson","year":"1987","unstructured":"Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF. 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Private funding partners include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer Inc. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health, USA. All OAI participants provided written informed consent for participation in the OAI. Ethics approval was obtained by each OAI clinical site (University of Maryland Baltimore -Institutional Review Board, Ohio State University\u2019s Biomedical Sciences Institutional Review Board, University of Pittsburgh Institutional Review Board, and Memorial Hospital of Rhode Island Institutional Review Board) and the OAI coordinating center (Committee on Human Research at the University of California, San Francisco, CA, USA [#10-00532]). For the NFOAS cohort, the ethics approval was from the Health Research Ethics Board of Newfoundland and Labrador [HREB #2011.311]. The Institutional Ethics Committee Board of the University of Montreal Hospital Research Centre [#BD04.001] approved the use of the human serum.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"120"}}