Csf1r⁻ macrophages govern the second wave of neutrophils for bone repair

Csf1r⁻ macrophages govern the second wave of neutrophils for bone repair | 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 Biological Sciences - Article Csf1r⁻ macrophages govern the second wave of neutrophils for bone repair Yasuhiro Kobayashi, Zhifeng He, Linan Shi, Yuko Nakamichi, Kohei Murakami, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6695752/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Macrophages play a pivotal role in tissue regeneration, including bone healing; however, the mechanisms and cell types through which they establish regenerative niches are not yet fully understood. Here, we identified a distinct subset of osteodirective macrophages (OdMacs), characterized by the expression profile F4/80⁺ Csf1r⁻ Cx3cr1hi Ccr2hi, which contribute to the formation of bone regenerative niches following injury. Histological analysis and FACS analysis, combined with transcriptomic profiling (RNA-seq and scRNA-seq), revealed that OdMacs facilitate the recruitment of activin A-expressing preneutrophils (preNeu) to sites of bone injury. This recruitment enhances the proliferation and osteogenic differentiation of LepR⁺ bone marrow stromal cells (BMSCs), thereby promoting bone regeneration. Furthermore, genetic studies using Axin2-Cre; tdTomato, Inhba, and Wls conditional knockout mice underscored the essential roles of Wnt signaling in BMSCs and preNeu-derived activin A in orchestrating this regenerative process. The OdMac-regulated regenerative niche represents a promising therapeutic target for regenerative medicine. Biological sciences/Immunology/Osteoimmunology Biological sciences/Cell biology/Cell migration/Mesenchymal migration Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Heetal.05192025SFig.pdf Extended Figs Cite Share Download PDF Status: Under Review 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6695752","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":458740627,"identity":"c74ce4a2-43c2-4e7d-8eec-69c73ae8fd97","order_by":0,"name":"Yasuhiro 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