{"doi":"10.1101/2022.03.08.479741","title":"Cell Surface-Bound La Protein Regulates The Cell Fusion Stage Of Osteoclastogenesis","abstract":"Abstract Multinucleated osteoclasts, essential for skeletal remodeling in health and diseases, are formed by fusion of osteoclast precursors with each fusion event raising their bone-resorbing activity. Here we report that nuclear RNA chaperone, La protein moonlights as an osteoclast fusion regulator. Monocyte-to-osteoclast differentiation starts with a drastic decrease in La levels. Then La reappears as a proteasecleaved species at the cell surface where it promotes fusion by mechanisms independent of La-RNA interactions. Appearance-and-disappearance of cell-surface La act as an on-and-off switch of the fusion activity with fusion slowing down when surface La is replaced in mature osteoclasts by full-length nuclear La. Inhibiting surface La in a novel explant model of fibrous dysplasia inhibits excessive osteoclast formation characteristic of this disease, highlighting La’s potential as a therapeutic target. One-Sentence Summary A nuclear RNA chaperon moves to the surface of osteoclasts to control their formation and function in bone metabolism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302877,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":658134,"name":"Evgenia Leikina","orcid":"0009-0001-5172-5963","position":1,"is_corresponding":false},{"id":658135,"name":"Kamran Melikov","orcid":"0009-0009-6523-4346","position":2,"is_corresponding":false},{"id":335186,"name":"Luis F de Castro","orcid":"0000-0003-3194-9780","position":3,"is_corresponding":false},{"id":373439,"name":"Sandy Mattijssen","orcid":"0000-0002-4285-7438","position":4,"is_corresponding":false},{"id":373440,"name":"Richard J Maraia","orcid":"0000-0002-5209-0066","position":5,"is_corresponding":false},{"id":298517,"name":"Michael T. Collins","orcid":"0000-0003-3676-7644","position":6,"is_corresponding":false},{"id":637776,"name":"Leonid Chernomordik","orcid":"0000-0001-7131-9244","position":7,"is_corresponding":false},{"id":637775,"name":"Jarred M. Whitlock","orcid":"0000-0002-5886-2047","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:20.348385Z","pmid":null,"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":[]}