Age- and Sex-Specific Deterioration on Bone and Osteocyte Lacuno-Canalicular Network in a Mouse Model of Premature Aging

Age- and Sex-Specific Deterioration on Bone and Osteocyte Lacuno-Canalicular Network in a Mouse Model of Premature Aging | 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 Age- and Sex-Specific Deterioration on Bone and Osteocyte Lacuno-Canalicular Network in a Mouse Model of Premature Aging Ralph Mueller, Dilara Yilmaz, Francisco Correia Marques, Lorena Gregorio, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4646934/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 May, 2025 Read the published version in Bone Research → Version 1 posted You are reading this latest preprint version Abstract Age-related osteoporosis poses a significant challenge in musculoskeletal health; a condition characterized by reduced bone density and increased fracture susceptibility in older individuals necessitates a better understanding of underlying molecular and cellular mechanisms. Emerging evidence suggests that osteocytes are the pivotal orchestrators of bone remodeling and represent novel therapeutic targets for age-related bone loss. Our study uses the prematurely aged PolgD257A/D257A (PolgA) mouse model to scrutinize age- and sex-related alterations in musculoskeletal health parameters (frailty, grip strength, gait data), bone and particularly the osteocyte lacuno-canalicular network (LCN). Moreover, we introduced a novel staining method for undecalcified fresh frozen bone sections along with a new quantitative in silico image analysis pipeline to evaluate the alterations in the osteocyte network with aging. Our findings underscore the pronounced degenerative changes in the musculoskeletal health parameters, bone and osteocyte LCN in PolgA mice as early as 40 weeks with more prominent alterations evident in aged males. Our findings suggest that the PolgA mouse model serves as a valuable model for studying the cellular mechanisms underlying age-related bone loss, given the comparable aging signs and age-related degeneration of the bone and the osteocyte network observed in naturally aging mice and elderly humans. Biological sciences/Physiology/Bone Biological sciences/Physiology/Bone quality and biomechanics Biological sciences/Physiology/Metabolism/Mitochondria Full Text Additional Declarations (Not answered) Supplementary Files Polg40wMWT.avi Representative wild type (WT) mouse osteocyte and dendrites at 40 week Polg40wFhomo.avi Representative PolgA mouse lacuno canalicular network (LCN) at 40 week SupplementaryFigureandTable.docx Supplementary Figures in the manuscript ocyprep.zip Pyhton code and the associated documents for osteocyte and LCN analysis SupVideos.pptx Osteocyte and lacuno canalicular network (LCN) in PolgA and WT mice Cite Share Download PDF Status: Published Journal Publication published 23 May, 2025 Read the published version in Bone Research → 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. 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