{"doi":"10.1007/s10067-020-05554-x","title":"Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1","abstract":null,"journal":"Clinical Rheumatology","year":2021,"id":627918,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1238553,"name":"Kaichi Kaneko","orcid":"0000-0002-2082-6948","position":1,"is_corresponding":false},{"id":1625466,"name":"Toshihiro Nanki","orcid":"0000-0002-3482-074X","position":2,"is_corresponding":false},{"id":1625465,"name":"Mai Kawazoe","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1","abstract":"<h4>Objective</h4>Our previous study suggested that suppression of Wnt/β-catenin signaling by increasing serum Wnt co-receptor inhibitors, sclerostin and Dickkopf-1, impairs bone formation in the first week after starting glucocorticoid therapy. The objective of this study was to investigate the involvement of the Wnt/β-catenin signaling pathway and its clinical significance in the subsequent suppression of bone formation.<h4>Methods</h4>A total of 53 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of Wnt3a and Wnt inhibitors, secreted Frizzled-related protein 1 (sFRP-1) and Wnt inhibitory factor 1 (Wif-1), before starting glucocorticoid therapy and every week for 4 weeks after its initiation.<h4>Results</h4>Serum levels of sFRP-1 and Wif-1 slightly decreased compared with before glucocorticoid therapy from the second week. The serum Wnt3a level decreased from the first week. The ratios of Wnt3a to sFRP-1 and that of Wnt3a to Wif-1 both decreased from the first week onward.<h4>Conclusion</h4>The reduction of the ratio of Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1, suppresses Wnt signaling, which may result in impaired bone formation. Taken together with our previous studies, glucocorticoids may suppress Wnt signaling by inhibiting co-receptors of the Wnt/β-catenin signaling pathway in the early phase of glucocorticoid therapy and inhibiting its ligand in the subsequent weeks, which together impair bone formation. Key Points • The decrease in Wnt pathway-related molecules by glucocorticoids impairs bone formation. • Glucocorticoids inhibit co-receptors of Wnt signaling in the early phase of therapy. • Glucocorticoids inhibit ligands of Wnt signaling in the subsequent phase of therapy.","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33420868","pmcid":null,"openalex_id":"https://openalex.org/W3120612646","authors":[],"funders":[{"funder_name":"a Project Research Grant from Toho University School of Medicine","grant_id":"17-12","title":null},{"funder_name":"a Project Research Grant from Toho University School of Medicine","grant_id":"18-26","title":null},{"funder_name":"a Research Promotion Grant from Toho University Graduate School of Medicine","grant_id":"17-01","title":null},{"funder_name":"the Program for the Strategic Research Foundation for Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology, Japan","grant_id":"S1411015","title":null},{"funder_name":"the Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science, and Technology, Japan","grant_id":"","title":null},{"funder_name":"the Nukada scholarship for Medical Research from Toho University School of Medicine","grant_id":"","title":null}],"total_grants":6,"fwci":1.0362,"citation_percentile":0.7445385,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":3}],"oa_status":"closed","license":"https://www.springer.com/tdm","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s10067-020-05554-x.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s10067-020-05554-x/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10067-020-05554-x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33420868","host_type":"repository"}],"fields_of_study":["Wnt/β-catenin signaling in development and cancer","Bone health and osteoporosis research","Connective Tissue Growth Factor Research"],"mesh_terms":["Frizzled-Related Proteins","Autoimmune Diseases","Glucocorticoids","Humans","Prednisolone","Intracellular Signaling Peptides and Proteins","Adaptor Proteins, Signal Transducing","Wnt Signaling Pathway","Wnt3A Protein"],"keywords":["WNT3A","Wnt signaling pathway","Sclerostin","Frizzled","Endocrinology","Internal medicine","LRP5","Medicine","LRP6","Glucocorticoid receptor","Glucocorticoid","Signal transduction","Beta-catenin","Catenin","Cancer research","Biology","Cell biology","Glucocorticoid-induced Osteoporosis","Wnt signaling","WIF-1","Sfrp-1"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T09:54:35.995691Z","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":[]}