Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29547667", "kind": "science-record", "revision": 7, "content_hash": "sha256:8d24d223f766e7fbf9b12a72070c8e9833d44497b3fb40b68165139180e7aab1", "created_at": "2026-11-01T15:40:32Z", "updated_at": "2026-11-01T21:59:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.", "doi": "10.1371/journal.pone.0194591", "pmid": "29547667", "authors": ["Christelle Sanchez", "Gabriel Mazzucchelli", "Cécile Lambert", "Fanny Comblain", "Edwin DePauw", "Yves Henrotin"], "journal": "PloS one", "year": 2018, "abstract": "OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone.\nDESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients. Finally, osteomodulin and fibulin-3 sequences were quantified by western blot and immunoassays in serum and culture supernatants.\nRESULTS: 175 proteins were identified in NSC osteoblast secretome. Data are available via ProteomeXchange with identifier PXD008494. Compared to NSC osteoblast secretome, 12 proteins were significantly less secreted (Osteomodulin, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 13 proteins were significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1, CSF-1). Similar changes in osteomodulin, IGF2, SERPINE1, fibulin-3 and CHI3L1 mRNA levels were observed. ELISAs assays confirm the decrease by half of osteomodulin protein in SC osteoblasts supernatant compared to NSC and in OA patients serum compared to healthy subjects. Fibulin-3 epitopes Fib3-1, Fib3-2 and Fib3-3 were also increased in SC osteoblasts supernatant compared to NSC.\nCONCLUSIONS: We highlighted some proteins differentially secreted by the osteoblasts coming from OA subchondral bone sclerosis. These changes contribute to explain some features observed in OA subchondral bone, like the increase of bone remodeling or abnormalities in bone matrix mineralization. Among identified proteins, osteomodulin was found decreased and fibulin-3 increased in serum of OA patients. These findings suggest that osteomodulin and fibulin-3 fragments could be biomarkers to monitor early changes in subchondral bone metabolism in OA.", "claims": [{"id": "claim-method", "statement": "A unpaired t-test was performed for each experiment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29547667", "locator": "sections[11] \"Statistical analysis\" paragraph 3", "quote": "A unpaired t-test was performed for each experiment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD008494 [12].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29547667", "locator": "sections[6] \"PLGS analysis\" paragraph 5", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD008494 [12]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study found 12 proteins less secreted and 13 more secreted by sclerotic-area osteoblasts, with osteomodulin decreased and fibulin-3 increased in OA serum; gene-expression and culture-supernatant ELISA data were analyzed by unpaired t-test, while serum western-blot and ELISA data underwent normality testing followed by Mann–Whitney tests or Spearman correlation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29547667", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Compared to NSC osteoblast secretome, 12 proteins were significantly less secreted (Osteomodulin, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 13 proteins were significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1, CSF-1)."}, {"asset": "source:pmid:29547667", "locator": "sections[11] \"Statistical analysis\" paragraph 3", "quote": "For gene expression and ELISA, the results (mean ± SD) were expressed as HPRT-normalized gene expression or as concentration of protein per μg of DNA. A unpaired t-test was performed for each experiment. For western-blot and ELISA quantification in sera, following a D'Agostino & Pearson omnibus normality test, a Mann-Whitney test or Spearman correlation was performed (GraphPad Prism 6.0)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study found 12 proteins less secreted and 13 more secreted by sclerotic-area osteoblasts, with osteomodulin decreased and fibulin-3 increased in OA serum; gene-expression and culture-supernatant ELISA data were analyzed by unpaired t-test, while serum western-blot and ELISA data underwent normality testing followed by Mann–Whitney tests or Spearman correlation.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29547667"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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In this study, we used a proteomic approach to compare secretome of osteoblast", "sted in Table 1. Five patients were used for mass spectrometry-based identification and 5 others patients f", "by NSC or SC osteoblasts were analyzed by LC-ESI-MS/MS, western blot or immunoassays. Cells were", "ported [7]. Further, before inclusion in the proteomic analysis, phenotype difference between SC an"], "order_basis": "paper_text_order:256", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n and fibulin-3 sequences were quantified by western blot and immunoassays in serum and culture supern", "irmatory analysis of selected proteins using western blot and immunoassays. The age of the patients ra", "C osteoblasts were analyzed by LC-ESI-MS/MS, western blot or immunoassays. Cells were collected and RN"], "order_basis": "paper_text_order:695", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["mentations, osteoblasts were rinsed and then cultured in a BSA/FBS free medium for 72 hours. The nutr"], "order_basis": "paper_text_order:4485", "id": "assay:3"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["order of magnitude. 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