Single-cell analysis reveals OSM-mediated osteogenic differentiation in Kashin-Beck disease bone hyperplasia

Single-cell analysis reveals OSM-mediated osteogenic differentiation in Kashin-Beck disease bone hyperplasia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Single-cell analysis reveals OSM-mediated osteogenic differentiation in Kashin-Beck disease bone hyperplasia Zongke Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7414397/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Kashin-Beck Disease (KBD) is an endemic degenerative osteoarthropathy that was historically widespread across China. The disease is characterized by early-stage cartilage necrosis followed by late-stage bone hyperplasia and joint deformity. Although preventive measures like improved water sources and grain substitution have effectively controlled new pediatric cases, many advanced-stage patients still suffer from progressive bone hyperplasia without effective treatment options. Through single-cell RNA sequencing of clinical specimens from late-stage KBD, osteoarthritis and normal subchondral bone, we identified an expanded population of mesenchymal lineage cells with enhanced osteogenic differentiation potential in KBD. Cell communication analysis revealed significant activation of the oncostatin M (OSM) signaling pathway in KBD, which was validated by elevated expression of OSM in myeloid cells and its receptor in mesenchymal-osteoblastic cells. In vitro studies confirmed that T-2 toxin-stimulated RAW264.7 secreted OSM, which promoted osteogenic differentiation of BMSCs. Importantly, pharmacological inhibition of OSM effectively attenuated bone hyperplasia in a rat model of late-stage KBD. Health sciences/Diseases/Rheumatic diseases/Musculoskeletal abnormalities Health sciences/Rheumatology/Musculoskeletal system/Bone Full Text Additional Declarations There is NO Competing Interest. Supplementary Files suptables.xlsx Sup table Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7414397","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":508619944,"identity":"5cc41981-9497-430c-ad61-dfe1caa58b4a","order_by":0,"name":"Zongke Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYJACxgYGGx5+9gbStKTJSPYcIE3LYRuDGw5EKpdv7z38ckbFeR6GGwyMHz7mEGNDz7k0yw1nbvMwzm5glpy5jQgtzBI5ZoYP227zMMscYGPmJUYLG1jLv3M8bBIJRGrhkcgxfrix4QAPD9FaJHjOmDHOOJbMI8FzsJk4v8i39xh/7Kmxs7c/3nzww0ditDCAvAOhgdFDLGD+QLTSUTAKRsEoGJkAAJjwNEL66R0/AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-8091-0474","institution":"Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Zongke","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2025-08-20 07:10:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7414397/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7414397/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93061121,"identity":"d41a4f1d-f2e2-4384-aad5-516424d26cae","added_by":"auto","created_at":"2025-10-08 16:12:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2248672,"visible":true,"origin":"","legend":"","description":"","filename":"SinglecellanalysisrevealsOSMmediatedosteogenicdifferentiationinKashinBeckdiseasebonehyperplasia.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7414397/v1_covered_ccb8bc03-9131-4880-9d96-6653f9698ad1.pdf"},{"id":90525283,"identity":"ddd21d74-de14-4d3e-913f-909d765f18cb","added_by":"auto","created_at":"2025-09-03 16:53:26","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":59849,"visible":true,"origin":"","legend":"Sup table","description":"","filename":"suptables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7414397/v1/901edc671d7993fc8ba9e5a8.xlsx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Single-cell analysis reveals OSM-mediated osteogenic differentiation in Kashin-Beck disease bone hyperplasia","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7414397/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7414397/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eKashin-Beck Disease (KBD) is an endemic degenerative osteoarthropathy that was historically widespread across China. 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