{"doi":"10.1359/jbmr.090411","title":"Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/β-catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/β-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost−/− mice were resistant to mechanical unloading-induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/β-catenin signaling was not altered by unloading in Sost−/− mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/β-catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.</jats:p>","journal":"Journal of Bone and Mineral Research","year":2009,"id":673086,"datarank":0.9661419810949383,"base_score":6.440946540632921,"endowment":6.440946540632921,"self_citation_contribution":0.9661419810949383,"citation_network_contribution":0.0,"self_endowment_contribution":0.9661419810949383,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":626,"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":844367,"name":"Xuan Jiang","orcid":"0000-0001-7802-0165","position":1,"is_corresponding":false},{"id":1206147,"name":"Zhongquan Dai","orcid":"0000-0002-6152-6407","position":2,"is_corresponding":false},{"id":1116099,"name":"Xizhi Guo","orcid":"0000-0001-8047-6049","position":3,"is_corresponding":false},{"id":1758598,"name":"Tujun Weng","orcid":null,"position":4,"is_corresponding":false},{"id":242464,"name":"Jun Wang","orcid":"0000-0002-8104-7470","position":5,"is_corresponding":false},{"id":1365361,"name":"Yinghui Li","orcid":"0000-0001-9271-4112","position":6,"is_corresponding":false},{"id":1260860,"name":"Guoyin Feng","orcid":null,"position":7,"is_corresponding":false},{"id":1170113,"name":"Xiang Gao","orcid":"0000-0002-0131-7857","position":8,"is_corresponding":false},{"id":609060,"name":"Lin He","orcid":"0000-0001-7437-1443","position":9,"is_corresponding":false},{"id":357247,"name":"Chuwen Lin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/β-catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/β-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost−/− mice were resistant to mechanical unloading-induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/β-catenin signaling was not altered by unloading in Sost−/− mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/β-catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19419300","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1359%2Fjbmr.090411","host_type":"publisher"},{"url":"https://academic.oup.com/jbmr/article-pdf/24/10/1651/56575316/5650241005.pdf","host_type":"publisher"}],"fields_of_study":["Adaptor Proteins, Signal Transducing","Animals","Animals, Newborn","Apoptosis","Bone Morphogenetic Proteins","Bone Resorption","Bone and Bones","Gene Deletion","Gene Targeting","Genetic Markers","Glycoproteins","Intercellular Signaling Peptides and Proteins","Mice","Models, Biological","Organ Size","Osteoblasts","Osteocytes","Osteogenesis","Signal Transduction","Stress, Mechanical","Up-Regulation","Wnt Proteins","beta Catenin"],"mesh_terms":["Bone and Bones","Osteoblasts","Osteocytes","Animals","Animals, Newborn","Mice","Bone Resorption","Glycoproteins","Intercellular Signaling Peptides and Proteins","Adaptor Proteins, Signal Transducing","Bone Morphogenetic Proteins","Genetic Markers","Organ Size","Gene Targeting","Signal Transduction","Apoptosis","Up-Regulation","Gene Deletion","Osteogenesis","Stress, Mechanical","Models, Biological","Wnt Proteins","beta Catenin"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T12:19:21.797945Z","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":[]}