{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:58:11Z","timestamp":1775059091329,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Resources from INR-LGII"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg\/dL) and MSU crystals (1, 5, and 10 \u03bcg\/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1\u03b2 and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 \u00b1 8%) and CD105 (52 \u00b1 18%) antigens, with 53 \u00b1 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg\/dL UA and 5 \u03bcg\/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 \u03bcg\/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2.<\/jats:p>","DOI":"10.3390\/medicina58121724","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T02:29:23Z","timestamp":1669343363000},"page":"1724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Osteogenic Potential of Monosodium Urate Crystals in Synovial Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"58","author":[{"given":"Karina","family":"Mart\u00ednez-Flores","sequence":"first","affiliation":[{"name":"Laboratorio de L\u00edquido Sinovial, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Plata-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, UNAM, Circuito Exterior S\/N, Coyoac\u00e1n, Cd. Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-0945","authenticated-orcid":false,"given":"Anell","family":"Olivos-Meza","sequence":"additional","affiliation":[{"name":"Servicio de Ortopedia del Deporte y Artroscop\u00eda, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-7424","authenticated-orcid":false,"given":"Ambar","family":"L\u00f3pez-Macay","sequence":"additional","affiliation":[{"name":"Laboratorio de L\u00edquido Sinovial, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Fern\u00e1ndez-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de L\u00edquido Sinovial, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0680-8516","authenticated-orcid":false,"given":"Carlos","family":"Landa-Sol\u00eds","sequence":"additional","affiliation":[{"name":"Unidad de Ingenier\u00eda de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-3454","authenticated-orcid":false,"given":"Yessica","family":"Zamudio-Cuevas","sequence":"additional","affiliation":[{"name":"Laboratorio de L\u00edquido Sinovial, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1097\/RHU.0000000000001121","article-title":"Multiarticular deforming and erosive tophaceous gout with severe comorbidities","volume":"26","author":"Anghelescu","year":"2019","journal-title":"J. Clin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5684","DOI":"10.1038\/s41598-021-84980-6","article-title":"Presence of tophi is associated with a rapid decline in the renal function in patients with gout","volume":"11","author":"Oh","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e18431","DOI":"10.1097\/MD.0000000000018431","article-title":"Relationship between urate within tophus and bone erosion according to the anatomic location of urate deposition in gout: A quantitative analysis using dual-energy CT volume measurements","volume":"98","author":"Shi","year":"2019","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/rheumatology\/ket329","article-title":"Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: New insights from a 3 T MRI study","volume":"53","author":"McQueen","year":"2014","journal-title":"Rheumatol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/art.23488","article-title":"Enhanced osteoclastogenesis in patients with tophaceous gout: Urate crystals promote osteoclast development through interactions with stromal cells","volume":"58","author":"Dalbeth","year":"2008","journal-title":"Arthritis. Rheum."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1136\/ard.2010.144774","article-title":"Monosodium urate monohydrate crystals inhibit osteoblast viability and function: Implications for development of bone erosion in gout","volume":"70","author":"Chhana","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13075-018-1704-y","article-title":"Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state","volume":"20","author":"Chhana","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_8","first-page":"756","article-title":"Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner","volume":"7","author":"Yang","year":"2012","journal-title":"Neural. Regen. Res."},{"key":"ref_9","first-page":"39","article-title":"The Effects of Uric Acid on Bone Mesenchymal Stem Cells Osteogenic Differentiation","volume":"4","author":"Xu","year":"2017","journal-title":"J. Appl. Sci. Eng. Innov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/jbt.21707","article-title":"Uric Acid Promotes Osteogenic Differentiation and Inhibits Adipogenic Differentiation of Human Bone Mesenchymal Stem Cells","volume":"29","author":"Li","year":"2015","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_12","first-page":"94","article-title":"Accuracy of lachman and anterior drawer tests for anterior cruciate ligament injuries","volume":"1","author":"Makhmalbaf","year":"2013","journal-title":"Arch. Bone Jt. Surg."},{"key":"ref_13","unstructured":"Stemcell Technologies (2022, August 22). Technical Manual: Human Colony-Forming Unit (CFU) Assays Using MethoCultTM. 2019. (Document #28404\/Version 4.6.0). Available online: https:\/\/cdn.stemcell.com\/media\/files\/manual\/MA28404-Human_Colony_Forming_Unit_Assays_Using_MethoCult.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0022-1759(84)90147-9","article-title":"Comparison of in vitro cell cytotoxic assays for tumor necrosis factor","volume":"68","author":"Flick","year":"1984","journal-title":"J. Immunol. Methods."},{"key":"ref_15","first-page":"71","article-title":"Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations","volume":"121","author":"Lanaspa","year":"2013","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13075-016-1012-3","article-title":"Monosodium urate crystals induce oxidative stress in human synoviocytes","volume":"18","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_17","first-page":"505","article-title":"Corrigendum to Normalization of data for viability and relative cell function curves","volume":"36","author":"Krebs","year":"2019","journal-title":"ALTEX Altern to Anim Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/jcb.22768","article-title":"Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes","volume":"111","author":"Arufe","year":"2010","journal-title":"J. Cell Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.14712\/fb2011057030119","article-title":"Isolation and characterization of synovial mesenchymal stem cells","volume":"57","author":"Rosocha","year":"2011","journal-title":"Folia Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1007\/s11033-021-07051-z","article-title":"Synovial membrane mesenchymal stem cells for cartilaginous tissues repair","volume":"49","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s12015-017-9753-1","article-title":"Mesenchymal Stem\/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives","volume":"13","author":"Huang","year":"2017","journal-title":"Stem. Cell Rev. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/art.21212","article-title":"Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source","volume":"52","author":"Sakaguchi","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/jor.20786","article-title":"Mesenchymal stem cells derived from synovium, meniscus, anterior cruciate ligament, and articular chondrocytes share similar gene expression profiles","volume":"27","author":"Segawa","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12917-015-0531-5","article-title":"Characterization of mesenchymal stem cells derived from the equine synovial fluid and membrane","volume":"11","author":"Prado","year":"2015","journal-title":"BMC Vet. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1155\/2017\/9312329","article-title":"Isolation and Characterization of Synovial Mesenchymal Stem Cell Derived from Hip Joints: A Comparative Analysis with a Matched Control Knee Group","volume":"2017","author":"Hatakeyama","year":"2017","journal-title":"Stem. Cells Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/cbin.10903","article-title":"Isolation and characterization of human mesenchymal stem cells derived from synovial fluid by magnetic-activated cell sorting (MACS)","volume":"42","author":"Jia","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/1535370219830665","article-title":"Phagocytosis of monosodium urate crystals by human synoviocytes induces inflammation","volume":"244","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12950-015-0070-7","article-title":"Role of the NLRP3 inflammasome in the transient release of IL-1\u03b2 induced by monosodium urate crystals in human fibroblast-like synoviocytes","volume":"12","author":"Zheng","year":"2015","journal-title":"J. Inflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39884","DOI":"10.1038\/srep39884","article-title":"Soluble Uric Acid Activates the NLRP3 Inflammasome","volume":"7","author":"Braga","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/annrheumdis-2014-205409","article-title":"Role of miR-146a in regulation of the acute inflammatory response to monosodium urate crystals","volume":"74","author":"Dalbeth","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"888306","DOI":"10.3389\/fimmu.2022.888306","article-title":"Inflammatory Response to Regulated Cell Death in Gout and Its Functional Implications","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/jcb.29272","article-title":"The effects of hyperuricemia on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells are implicated in the elevated risk of osteopenia and vascular calcification in gout: An in vivo and in vitro analysis","volume":"120","author":"Yan","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s13075-022-02900-z","article-title":"Factors secreted by monosodium urate crystal-stimulated macrophages promote a proinflammatory state in osteoblasts: A potential indirect mechanism of bone erosion in gout","volume":"24","author":"Naot","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"809586","DOI":"10.3389\/fimmu.2022.809586","article-title":"The Inhibition of Osteoblast Viability by Monosodium Urate Crystal-Stimulated Neutrophil-Derived Exosomes","volume":"13","author":"Jia","year":"2022","journal-title":"Front. Immunol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/12\/1724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:26:09Z","timestamp":1760145969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/12\/1724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["medicina58121724"],"URL":"https:\/\/doi.org\/10.3390\/medicina58121724","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}