{"doi":"10.1101/2025.05.12.653519","title":"LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-κβ-Induced Chondrocyte Apoptosis","abstract":"Abstract Temporomandibular joint osteoarthritis (TMJ-OA) affects a significant proportion of the population worldwide. However, there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms. Lysyl Oxidase Like-2 (LOXL2) promotes knee joint cartilage protection, and it is downregulated in TMJ-OA animal model. We evaluated the role of LOXL2 in TMJ cartilage, its molecular mechanism and gene networks using in vivo Loxl2 knockout mice ( Acan-Cre; Loxl2 flox/flox ) and ex vivo goat TMJ cartilage. Our results show that Loxl2 knockout in mice cartilage upregulates Il1b, Mmp9, Mmp13, Adamts4 , and Adamts5 , whereas it reduces the levels of aggrecan and proteoglycan. Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response, TNFA signaling via NF-kB, extracellular matrix (ECM), and collagen degradation pathway network. Conversely, LOXL2 treatment reduces interleukin-1 beta (IL-1β)-induced expression of Mmp13 , protects mitochondrial function and ECM from degeneration. Importantly, LOXL2 attenuates IL-1β-induced chondrocyte apoptosis via phosphorylation of NF-κB and expression of pain-related gene PTGS2 (encodes COX2). Taken together, Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation, mitochondrial dysfunction, chondrocyte apoptosis, and inflammatory gene expression, whereas LOXL2 treatment mitigates these effects. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565820,"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":0.954,"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":1469355,"name":"Chumki Choudhury","orcid":"0009-0004-0412-7161","position":1,"is_corresponding":false},{"id":1469356,"name":"Faiza Ali","orcid":"0009-0004-9535-3729","position":2,"is_corresponding":false},{"id":1368026,"name":"Amit Kumar Chakraborty","orcid":"0000-0001-7455-6579","position":3,"is_corresponding":false},{"id":1469357,"name":"Mohammed Moeeduddin Ahmed","orcid":"0000-0002-5865-2496","position":4,"is_corresponding":false},{"id":1469722,"name":"Cheyleann Del Valle-Ponce De Leon","orcid":null,"position":5,"is_corresponding":false},{"id":1469723,"name":"Harshal V. Modh","orcid":null,"position":6,"is_corresponding":false},{"id":495551,"name":"Pushkar Mehra","orcid":"0000-0002-9661-0289","position":7,"is_corresponding":false},{"id":1469358,"name":"Yuwei Fan","orcid":"0000-0001-8477-8458","position":8,"is_corresponding":false},{"id":530602,"name":"Alejandro J. Almarza","orcid":"0000-0003-4602-9258","position":9,"is_corresponding":false},{"id":411954,"name":"Manish V. Bais","orcid":"0000-0003-4198-7377","position":10,"is_corresponding":false},{"id":1368025,"name":"Rajnikant Raut","orcid":"0000-0001-6963-5889","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40463059","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":[]}