{"doi":"10.1172/jci.insight.131382","title":"Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation","abstract":"Extracellular matrix and osmolarity influence the development and homeostasis of skeletal tissues through Rho GTPase-mediated alteration of the actin cytoskeleton. This study investigated whether the actin-branching Arp2/3 complex, a downstream effector of the Rho GTPases Cdc42 and Rac1, plays a critical role in maintaining the health of matrix-rich and osmotically loaded intervertebral discs and cartilage. Mice with constitutive intervertebral disc- and cartilage-specific deletion of the critical Arp2/3 subunit Arpc2 (Col2-Cre; Arpc2fl/fl) developed chondrodysplasia and spinal defects. Since these mice did not survive to adulthood, we generated mice with inducible Arpc2 deletion in disc and cartilage (Acan-CreERT2; Arpc2fl/fl). Inactivation of Arp2/3 at skeletal maturity resulted in growth plate closure, loss of proteoglycan content in articular cartilage, and degenerative changes in the intervertebral disc at 1 year of age. Chondrocytes with Arpc2 deletion showed compromised cell spreading on both collagen and fibronectin. Pharmacological inhibition of Cdc42 and Arp2/3 prevented the osmoadaptive transcription factor TonEBP/NFAT5 from recruiting cofactors in response to a hyperosmolarity challenge. Together, these findings suggest that Arp2/3 plays a critical role in cartilaginous tissues through the regulation of cell-extracellular matrix interactions and modulation of TonEBP-mediated osmoadaptation.","journal":"JCI Insight","year":2020,"id":98270,"datarank":0.519860385419959,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.0,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":485794,"name":"Alexandra C. Doolittle","orcid":null,"position":1,"is_corresponding":false},{"id":485000,"name":"Kimheak Sao","orcid":"0000-0002-9164-1529","position":2,"is_corresponding":false},{"id":485001,"name":"Jeremy D. Rotty","orcid":"0000-0002-7782-9672","position":3,"is_corresponding":false},{"id":453521,"name":"James E. Bear","orcid":"0000-0002-8489-996X","position":4,"is_corresponding":false},{"id":485795,"name":"Veronica Ulici","orcid":null,"position":5,"is_corresponding":false},{"id":404668,"name":"Richard F. Loeser","orcid":"0000-0003-2832-6144","position":6,"is_corresponding":false},{"id":266144,"name":"Irving M. Shapiro","orcid":"0000-0001-5799-6142","position":7,"is_corresponding":false},{"id":479511,"name":"Brian O. Diekman","orcid":"0000-0001-9055-4282","position":8,"is_corresponding":false},{"id":266145,"name":"Makarand V. Risbud","orcid":"0000-0003-3913-0649","position":9,"is_corresponding":false},{"id":484999,"name":"Steven Tessier","orcid":"0000-0003-1320-5286","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:36:34.157932Z","pmid":"31961823","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":[]}