{"doi":"10.1002/jsp2.70053","title":"Mechanism of Intervertebral Disc Degeneration via the β‐Catenin/<scp>CCL2</scp> Pathway in Sox9 Conditional Knockout Mice","abstract":"Introduction: Degenerative changes in the intervertebral disc (IVD) are known to be a main cause of low back pain (LBP), oftentimes necessitating interventions that may or may not be successful due to a lack of understanding in the degenerative phenotype and its mechanisms. Understanding the molecular mechanisms of disc degeneration can help design new therapies to induce disc regeneration and reduce back pain. This work aimed to understand the effects of conditional deletion of Sox9 in aggrecan-expressing cells on intervertebral disc degeneration and its underlying mechanisms in mice. Methods: mice to investigate the effects of SOX9 deletion on IVD degeneration and associated pain behaviors. Mice were administered tamoxifen to induce conditional gene deletion of Sox9. Structural and degenerative phenotypes of the spine were assessed by a histological scoring system and micro-computed tomography (microCT). Pain behaviors were evaluated through mechanical allodynia testing and the LABORAS system for spontaneous behavior assessment. Immunohistochemistry identified the expression of proteins of interest, which were further examined by Western blotting. Lastly, quantitative real-time PCR and promoter assays on IVD cells were used to examine inflammatory and signaling pathways induced by Sox9 deletion. Results: deletion also increased β-catenin, C-C motif chemokine ligand 2 (CCL2), and Glial cell line-derived neurotrophic factor (GDNF) expression in the IVD, suggesting their roles in disc pain and degeneration and the importance of the β-catenin/CCL2 pathway in these processes. Conclusions: in Aggrecan-expressing IVD tissues affects disc degeneration and associated pain behaviors through the β-catenin-CCL2 pathway. Such findings can lead to more targeted, personalized therapeutics in the future to address discogenic origins of LBP.","journal":"JOR Spine","year":2025,"id":525317,"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":0.9552,"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":1028296,"name":"Ana Chee","orcid":"0000-0002-7977-2737","position":1,"is_corresponding":false},{"id":354172,"name":"Frank C. Ko","orcid":"0000-0001-6532-2084","position":2,"is_corresponding":false},{"id":1062077,"name":"Jad Alkhudari","orcid":null,"position":3,"is_corresponding":false},{"id":759558,"name":"Saurav Sumughan","orcid":"0000-0001-5974-3835","position":4,"is_corresponding":false},{"id":761793,"name":"Howard S. An","orcid":"0000-0001-9560-9131","position":5,"is_corresponding":false},{"id":650910,"name":"Dino Samartzis","orcid":"0000-0002-7473-1311","position":6,"is_corresponding":false},{"id":234888,"name":"Chun‐do Oh","orcid":"0000-0002-5419-8011","position":7,"is_corresponding":false},{"id":1080955,"name":"Khaled Aboushaala","orcid":"0000-0002-4134-1464","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:50:21.274116Z","pmid":"40012719","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":[]}