{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:22:28Z","timestamp":1772518948148,"version":"3.50.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AG059923"],"award-info":[{"award-number":["AG059923"]}]},{"name":"NIH","award":["AR075803"],"award-info":[{"award-number":["AR075803"]}]},{"name":"NIH","award":["AR074473"],"award-info":[{"award-number":["AR074473"]}]},{"name":"NIH","award":["1S10OD032354"],"award-info":[{"award-number":["1S10OD032354"]}]},{"name":"NIH","award":["P20GM109095"],"award-info":[{"award-number":["P20GM109095"]}]},{"name":"NSF","award":["2025505"],"award-info":[{"award-number":["2025505"]}]},{"name":"NSF","award":["NSF1929188"],"award-info":[{"award-number":["NSF1929188"]}]},{"name":"TCNJ Mentored Undergraduate Summer Experience"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex serves to connect the nuclear envelope and the cytoskeleton, influencing cellular processes such as nuclear arrangement, architecture, and mechanotransduction. The role LINC plays in mechanotransduction pathways in bone progenitor cells has been well studied; however, the mechanisms by which LINC complexes govern\n                    <jats:italic>in vivo<\/jats:italic>\n                    bone formation remain less clear. To bridge this knowledge gap, we established a murine model disrupting LINC using transgenic Prx-Cre mice and floxed Tg(CAG-LacZ\/EGFP-KASH2) mice. Prx-Cre mice express the Cre recombinase enzyme controlled by the paired-related homeobox gene-1 promoter (\n                    <jats:italic>Prrx1<\/jats:italic>\n                    ), a pivotal regulator of skeletal development. Prx-Cre animals have been widely used in the bone field to target bone progenitor cells. Tg(CAG-LacZ\/EGFP-KASH2) mice carry a lox-stop-lox flanked LacZ gene allowing for the overexpression of an EGFP-KASH2 fusion protein via cre recombinase mediated deletion of the LacZ cassette. This disrupts endogenous Nesprin-Sun binding in a dominant negative manner disconnecting nesprin from the nuclear envelope. By combining these lines, we generated a Prrx1(+) cell-specific LINC disruption model to study its impact on the developing skeleton and subsequently exercise-induced bone accrual. The findings presented here indicate Prx-driven LINC disruption (PDLD) cells exhibit no change in osteogenic and adipogenic potential compared to controls\n                    <jats:italic>in vitro<\/jats:italic>\n                    nor are there bone quality changes when compared to in sedentary animals at 8 weeks. While PDLD animals displayed increased voluntary running activity andPrrx1(+) cell-specific LINC disruption abolished the exercise-induced increases in osteoid volume and surface after a 6-week exercise intervention, no other changes in bone microarchitecture or mechanical properties were found.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0307816","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T13:25:51Z","timestamp":1732109151000},"page":"e0307816","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prrx1-driven LINC complex disruption in vivo reduces osteoid deposition but not bone quality after voluntary wheel running"],"prefix":"10.1371","volume":"19","author":[{"given":"Scott","family":"Birks","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Howard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian S.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"O\u2019Rourke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elicza A.","family":"Day","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Lamb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Walsdorf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-4942","authenticated-orcid":true,"given":"Gunes","family":"Uzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"issue":"4","key":"pone.0307816.ref001","first-page":"299","article-title":"HOW DO BONE CELLS SENSE MECHANICAL LOADING?","volume":"44","author":"C.V. 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Padmakumar","year":"2005","journal-title":"J Cell Sci"},{"issue":"10","key":"pone.0307816.ref005","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1128\/MCB.26.10.3738-3751.2006","article-title":"SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton","volume":"26","author":"F. Haque","year":"2006","journal-title":"Mol Cell Biol"},{"key":"pone.0307816.ref006","doi-asserted-by":"crossref","first-page":"116023","DOI":"10.1016\/j.bone.2021.116023","article-title":"At the nuclear envelope of bone mechanobiology","volume":"151","author":"S. Birks","year":"2021","journal-title":"Bone"},{"issue":"6","key":"pone.0307816.ref007","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/stem.2004","article-title":"Cell Mechanosensitivity to Extremely Low\u2010Magnitude Signals Is Enabled by a LINCed Nucleus","volume":"33","author":"G. 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