{"doi":"10.3390/cells14120891","title":"Effects of Modified Messenger RNA of Adiponectin Delivered by Lipid Nanoparticles on Adipogenesis and Bone Metabolism In Vitro and In Vivo","abstract":"Adiponectin (APN) is a secreted adipokine that plays a key role in modulating energy and bone metabolism, as well as regulating inflammatory responses. The overexpression of APN has been proposed as a potential therapeutic strategy for treating obesity and related disorders. Lipid nanoparticles (LNPs) are promising vectors for transporting messenger ribonucleic acid (mRNA) molecules. This study tested whether delivering a stabilized version of adiponectin mRNA (APN mRNA) using lipid nanoparticles could reduce fat formation and promote bone repair in vitro and in vivo. We demonstrated that transfection with APN-LNP upregulated the mRNA and protein expression of APN, while inhibiting adipogenesis in 3T3-L1 adipocytes. APN-LNP enhanced osteogenic gene expression in MC3T3-E1 cells in a dose-dependent manner. It also reduced matrix metalloproteinase 9 expression in receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated RAW264.7 cells, suggesting an anti-resorptive effect. In vivo, a femoral fracture model was established to explore the application of APN-LNP in promoting bone healing in diet-induced obese mice. Micro-computed tomography and histology analysis indicated that intravenous injection with APN-LNP promoted bone healing. Fasting blood glucose and body weight were decreased in the APN-LNP group. Moreover, APN-LNP increased bone sialoprotein and runt-related transcription factor 2 expression in contralateral femurs, as well as interleukin-10 expression in white adipose tissues. Thus, our study provides promising preclinical data on the potential use of APN-LNP for treating bone disorders in obesity.","journal":"Cells","year":2025,"id":544783,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1435289,"name":"Qian Ma","orcid":"0000-0002-9680-3785","position":1,"is_corresponding":false},{"id":1071919,"name":"Jinghao Wang","orcid":"0009-0006-5666-9645","position":2,"is_corresponding":false},{"id":1072486,"name":"Zoe Xiaofang Zhu","orcid":null,"position":3,"is_corresponding":false},{"id":1071920,"name":"Rady E. El-Araby","orcid":"0000-0003-4822-5279","position":4,"is_corresponding":false},{"id":338412,"name":"Maxwell Tu","orcid":null,"position":5,"is_corresponding":false},{"id":494373,"name":"Zhongyu Li","orcid":"0000-0002-9566-5771","position":6,"is_corresponding":false},{"id":692031,"name":"Xiaoyang Xu","orcid":"0009-0003-7796-7690","position":7,"is_corresponding":false},{"id":310623,"name":"Qisheng Tu","orcid":"0000-0003-0639-8761","position":8,"is_corresponding":false},{"id":14606,"name":"Jake Y. Chen","orcid":"0000-0001-8829-7504","position":9,"is_corresponding":false},{"id":1435288,"name":"Ying Xie","orcid":"0000-0002-1787-5917","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40558518","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":[]}