{"doi":"10.1126/sciadv.abm9843","title":"Targeting TRPC channels for control of arthritis-induced bone erosion","abstract":"Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca 2+ -selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels. While ELP-004 minimally affected physiological RANKL-induced osteoclast maturation in murine bone marrow– and spleen-derived myeloid cells (BMSMCs) and human PBMC-derived cells, it potently interfered with osteoclast maturation driven by TNFα or LTB4. The contribution of TRPC channels to osteoclastogenesis was examined using BMSMCs derived from TRPC4 −/− or TRPC(1–7) −/− mice, again revealing preferential interference with osteoclastogenesis driven by proinflammatory cytokines. ELP-004 also reduced bone erosion in a mouse model of rheumatoid arthritis. These investigations reveal TRPC channels as critical mediators of inflammatory bone erosion and provide insight into the major target of ELP-004, a drug currently in preclinical testing as a therapeutic for inflammatory arthritis.","journal":"Science Advances","year":2025,"id":538486,"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":789968,"name":"Jamie L. McCall","orcid":"0000-0001-5914-6336","position":1,"is_corresponding":false},{"id":243367,"name":"Jinbin Tian","orcid":"0000-0002-5516-7778","position":2,"is_corresponding":false},{"id":409119,"name":"Jaepyo Jeon","orcid":"0000-0002-0275-7395","position":3,"is_corresponding":false},{"id":1388416,"name":"Aidan Douglas","orcid":null,"position":4,"is_corresponding":false},{"id":1425444,"name":"Kendall Tyler","orcid":null,"position":5,"is_corresponding":false},{"id":1425067,"name":"Siyao Liu","orcid":"0009-0000-0575-3835","position":6,"is_corresponding":false},{"id":1425068,"name":"Kendyl Berry","orcid":"0000-0001-8447-3881","position":7,"is_corresponding":false},{"id":1425069,"name":"Brady Nicewarner","orcid":"0009-0004-4342-0037","position":8,"is_corresponding":false},{"id":789969,"name":"Casey Hall","orcid":"0000-0002-4294-6131","position":9,"is_corresponding":false},{"id":144284,"name":"Klaus Groschner","orcid":"0000-0002-8659-377X","position":10,"is_corresponding":false},{"id":1425070,"name":"Bernadett Bacsa","orcid":"0000-0003-2201-4721","position":11,"is_corresponding":false},{"id":345346,"name":"Werner J. Geldenhuys","orcid":"0000-0002-2405-376X","position":12,"is_corresponding":false},{"id":243371,"name":"Michael X. Zhu","orcid":"0000-0002-5676-841X","position":13,"is_corresponding":false},{"id":424248,"name":"Harry C. Blair","orcid":"0000-0002-1152-3718","position":14,"is_corresponding":false},{"id":425761,"name":"John B. Barnett","orcid":"0000-0001-6547-2381","position":15,"is_corresponding":false},{"id":342726,"name":"Jonathan Soboloff","orcid":"0000-0001-5192-1297","position":16,"is_corresponding":false},{"id":1320540,"name":"Suravi Ray","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:52:21.389196Z","pmid":"39813349","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":[]}