{"doi":"10.3390/ijms23062938","title":"Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis","abstract":"Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.","journal":"International Journal of Molecular Sciences","year":2022,"id":268994,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"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":931709,"name":"Irma Josefina Savitri","orcid":"0000-0002-5847-6509","position":1,"is_corresponding":false},{"id":907999,"name":"Takenobu Ishii","orcid":"0000-0003-0654-1521","position":2,"is_corresponding":false},{"id":745822,"name":"Atsushi Ikeda","orcid":"0000-0001-8930-8121","position":3,"is_corresponding":false},{"id":908541,"name":"Roodelyne Pierrelus","orcid":null,"position":4,"is_corresponding":false},{"id":908002,"name":"Alireza Heidari","orcid":"0000-0002-5266-1041","position":5,"is_corresponding":false},{"id":932284,"name":"Keisuke Okubo","orcid":null,"position":6,"is_corresponding":false},{"id":908005,"name":"Shin Nakamura","orcid":"0000-0001-7427-8636","position":7,"is_corresponding":false},{"id":461068,"name":"Umadevi Kandalam","orcid":"0009-0008-3785-2908","position":8,"is_corresponding":false},{"id":696659,"name":"Mohamad Rawas-Qalaji","orcid":"0000-0002-5979-1930","position":9,"is_corresponding":false},{"id":908003,"name":"Elizabeth Leon","orcid":"0000-0002-4693-1973","position":10,"is_corresponding":false},{"id":908542,"name":"Maria Rita Pastore","orcid":null,"position":11,"is_corresponding":false},{"id":908007,"name":"Patrick C. Hardigan","orcid":"0000-0001-6965-1766","position":12,"is_corresponding":false},{"id":303716,"name":"Toshihisa Kawai","orcid":"0000-0003-3310-3818","position":13,"is_corresponding":false},{"id":908004,"name":"Satoru Shindo","orcid":"0000-0003-0478-9363","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:27:18.142851Z","pmid":"35328359","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":[]}