Long non-coding RNA Malat1 fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and the β-catenin-OPG/Jagged1 pathway

Long non-coding RNA Malat1 fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and the β-catenin-OPG/Jagged1 pathway | 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 Research Article Long non-coding RNA Malat1 fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and the β-catenin-OPG/Jagged1 pathway Baohong Zhao, Yongli Qin, Jumpei Shirakawa, Cheng Xu, Ruge Chen, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3793919/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract The IncRNA Malat1 was initially believed to be dispensable for physiology due to the lack of observable phenotypes in Malat1 knockout (KO) mice. However, our study challenges this conclusion. We found that both Malat1 KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis. Mechanistically, Malat1 acts as an intrinsic regulator in osteoblasts to promote osteogenesis. Interestingly, Malat1 does not directly affect osteoclastogenesis but inhibits osteoclastogenesis in a non-autonomous manner in vivo via integrating crosstalk between multiple cell types, including osteoblasts, osteoclasts and chondrocytes. Our findings substantiate the existence of a novel remodeling network in which Malat1 serves as a central regulator by binding to β-catenin and functioning through the β-catenin-OPG/Jagged1 pathway in osteoblasts and chondrocytes. In pathological conditions, Malat1 significantly promotes bone regeneration in fracture healing. Bone homeostasis and regeneration are crucial to well-being. Our discoveries establish a previous unrecognized paradigm model of Malat1 function in the skeletal system, providing novel mechanistic insights into how a lncRNA integrates cellular crosstalk and molecular networks to fine tune tissue homeostasis, remodeling and repair. Biological sciences/Cell biology Biological sciences/Molecular biology Malat1 bone fracture lncRNA long non-coding RNA homeostasis remodeling Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 3 posted You are reading this latest preprint version Show more versions 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. 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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-3793919","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298556325,"identity":"25b5c8d5-ee23-4823-9f31-a284208f0e63","order_by":0,"name":"Baohong Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAp0lEQVRIiWNgGAWjYDACCQYGZoaKAzA20VrOkKyFsY0ULfKzmx8+Lpx3x16+gfngbR5itDDOOWZsPHPbs8QNB9iSrYnSwiyRYCbNu+1wggEDj5k0UVrYJNK/SfPOOQx0GP834rTwSOQAbWk4zNhwgIeNOC0SEjnFxjOOHU7ccJjN2HIOMVrkZ6RvfFxQA3RYe/PDG2+I0YIAzKQpHwWjYBSMglGADwAAYtgtUTegf+0AAAAASUVORK5CYII=","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":true,"prefix":"","firstName":"Baohong","middleName":"","lastName":"Zhao","suffix":""},{"id":298556326,"identity":"ac00dfb3-f37f-4572-a4de-2a9ccf478c2d","order_by":1,"name":"Yongli Qin","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Yongli","middleName":"","lastName":"Qin","suffix":""},{"id":298556327,"identity":"516e3aa1-ec33-4702-9ee1-af43d1b8cf51","order_by":2,"name":"Jumpei Shirakawa","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Jumpei","middleName":"","lastName":"Shirakawa","suffix":""},{"id":298556328,"identity":"d0c0688c-e183-44eb-b7fe-211991ec23c2","order_by":3,"name":"Cheng Xu","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Xu","suffix":""},{"id":298556329,"identity":"417119b4-3a9a-46b4-9a84-7342ba191230","order_by":4,"name":"Ruge Chen","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Ruge","middleName":"","lastName":"Chen","suffix":""},{"id":363853220,"identity":"4d9f7842-edb6-47cd-bff1-e8bbc1d44725","order_by":5,"name":"Xu Yang","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Yang","suffix":""},{"id":298556330,"identity":"68a364e3-125e-43f2-a0cc-00050138770f","order_by":6,"name":"Courtney Ng","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Courtney","middleName":"","lastName":"Ng","suffix":""},{"id":298556331,"identity":"c01fe3cc-85a4-4c9a-afbc-56dcb6fe7c1e","order_by":7,"name":"Shinichi Nakano","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Shinichi","middleName":"","lastName":"Nakano","suffix":""},{"id":298556332,"identity":"d206679d-e1e9-404d-ac87-d482c1d68203","order_by":8,"name":"Mahmoud Elguindy","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Elguindy","suffix":""},{"id":298556333,"identity":"f08d779e-cac2-4ef0-a1e6-ca8ddd74a9bf","order_by":9,"name":"Zhonghao Deng","email":"","orcid":"","institution":"Hospital for Special Surgery","correspondingAuthor":false,"prefix":"","firstName":"Zhonghao","middleName":"","lastName":"Deng","suffix":""},{"id":298556334,"identity":"7f542f94-7ed3-403b-b30f-6dba40ed77be","order_by":10,"name":"Kannanganattu Prasanth","email":"","orcid":"","institution":"3.\tDepartment of Cell and Developmental Biology, Cancer center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA","correspondingAuthor":false,"prefix":"","firstName":"Kannanganattu","middleName":"","lastName":"Prasanth","suffix":""},{"id":298556335,"identity":"f4392359-f5ea-44a5-8b3b-0a186bdc76b7","order_by":11,"name":"Moritz Eissmann","email":"","orcid":"","institution":"4.\tInstitute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt, Germany","correspondingAuthor":false,"prefix":"","firstName":"Moritz","middleName":"","lastName":"Eissmann","suffix":""},{"id":298556336,"identity":"d0100462-327a-4be1-b237-2191f21ead5a","order_by":12,"name":"Shinichi Nakagawa","email":"","orcid":"https://orcid.org/0000-0002-6806-7493","institution":"Hokkaido University","correspondingAuthor":false,"prefix":"","firstName":"Shinichi","middleName":"","lastName":"Nakagawa","suffix":""},{"id":298556337,"identity":"b35ba84b-9a02-4f70-a305-4331cb45fe76","order_by":13,"name":"William M. 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