{"doi":"10.17615/j3fx-8v71","title":"Delayed fracture healing and increased callus adiposity in a C57BL/6J Murine model of obesity-associated type 2 diabetes mellitus","abstract":"Introduction: Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed. Methods: Male C57BL/6J mice at 5 weeks of age were placed on either a control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid-diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14, 21, 28, and 35 for micro-computed tomography (μCT), histology-based histomorphometry and molecular analyses, and biomechanical testing. Results: HFD-fed mice displayed increased body weight and impaired glucose tolerance, both characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia fractures showed significantly (p<0.001) decreased woven bone at day 28 by histomorphometry and significantly (p<0.01) decreased callus bone volume at day 21 by μCT. Interestingly, fracture calluses contained markedly increased adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed increased PPARγ immunohistochemical staining at day 14. Finally, calluses from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional rigidity compared to controls. Discussion: Our murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching.","journal":"UNC Libraries","year":2022,"id":311814,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1008578,"name":"H. Awad","orcid":null,"position":1,"is_corresponding":false},{"id":1008579,"name":"C.W. Farnsworth","orcid":null,"position":2,"is_corresponding":false},{"id":982096,"name":"D.-G. Chen","orcid":"0009-0005-1201-5546","position":3,"is_corresponding":false},{"id":1008580,"name":"M.L. Brown","orcid":null,"position":4,"is_corresponding":false},{"id":1008581,"name":"M.J. Hilton","orcid":null,"position":5,"is_corresponding":false},{"id":1008582,"name":"R.J. O apos Keefe","orcid":null,"position":6,"is_corresponding":false},{"id":1008583,"name":"K. Yukata","orcid":null,"position":7,"is_corresponding":false},{"id":1008584,"name":"M.J. Zuscik","orcid":null,"position":8,"is_corresponding":false},{"id":538116,"name":"L. Xing","orcid":null,"position":9,"is_corresponding":false},{"id":1008577,"name":"R.A. Mooney","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:32.327694Z","pmid":null,"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":[]}