{"doi":"10.1101/2023.08.24.554623","title":"Osterix-driven LINC complex disruption <i>in vivo</i> diminishes bone microarchitecture in 8-week male mice but not after 6-week voluntary wheel running","abstract":"Abstract The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a crucial connective component between the nuclear envelope and the cytoskeleton involving various cellular processes including nuclear positioning, nuclear architecture, and mechanotransduction. How LINC complexes regulate bone formation in vivo , however, is not well understood. To start bridging this gap, here we created a LINC disruption murine model using transgenic mice expressing Cre recombinase enzyme under the control of the Osterix (Osx-Cre) which is primarily active in pre-osteoblasts and floxed Tg(CAG-LacZ/EGFP-KASH2) mice. Tg(CAG-LacZ/EGFP-KASH2) mice contain a lox-STOP-lox flanked LacZ gene which is deleted upon cre recombination allowing for the overexpression of an EGFP-KASH2 fusion protein. This overexpressed protein disrupts endogenous Nesprin-Sun binding leading to disruption of LINC complexes. Thus, crossing these two lines results in a O sx- d riven L INC d isruption (ODLD) specific to pre-osteoblasts. In this study, we investigated how this LINC disruption affects exercise induced bone accrual. ODLD cells had decreased osteogenic and adipogenic potential in vitro compared to non-disrupted controls and sedentary ODLD mice showed decreased bone quality at 8-weeks. Upon access to a voluntary running wheel ODLD animals showed increased running time and distance; however, our 6-week exercise intervention did not significantly affect bone microarchitecture and bone mechanical properties.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395006,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":898586,"name":"Sean Howard","orcid":"0000-0001-7556-1951","position":1,"is_corresponding":false},{"id":1170334,"name":"Caroline O’Rourke","orcid":null,"position":2,"is_corresponding":false},{"id":442212,"name":"William R. Thompson","orcid":"0000-0002-7022-585X","position":3,"is_corresponding":false},{"id":773680,"name":"Anthony G. Lau","orcid":"0000-0002-1094-4289","position":4,"is_corresponding":false},{"id":348011,"name":"Gunes Uzer","orcid":"0000-0002-1178-4942","position":5,"is_corresponding":false},{"id":708850,"name":"Scott Birks","orcid":"0000-0002-3941-1240","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37662368","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}