Prrx1-driven LINC complex disruption in vivo reduces osteoid deposition but not bone quality after voluntary wheel running.

Autor: Birks S; Micron School of Materials Science and Engineering, Boise State University, Boise, Idaho, United States of America., Howard S; Mechanical and Biomedical Engineering, Boise State University, Boise, Idaho, United States of America., Wright CS; Department of Physical Therapy, Indiana University, Bloomington, Indiana, United States of America., O'Rourke C; Biomedical Engineering, The College of New Jersey, Ewing Township, New Jersey, United States of America., Day EA; Department of Physical Therapy, Indiana University, Bloomington, Indiana, United States of America., Lamb AJ; Department of Physical Therapy, Indiana University, Bloomington, Indiana, United States of America., Walsdorf JR; Department of Physical Therapy, Indiana University, Bloomington, Indiana, United States of America., Lau A; Biomedical Engineering, The College of New Jersey, Ewing Township, New Jersey, United States of America., Thompson WR; Department of Physical Therapy, Indiana University, Bloomington, Indiana, United States of America., Uzer G; Mechanical and Biomedical Engineering, Boise State University, Boise, Idaho, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Nov 20; Vol. 19 (11), pp. e0307816. Date of Electronic Publication: 2024 Nov 20 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0307816
Abstrakt: 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 in vivo 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 (Prrx1), 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 in vitro 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Birks et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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