{"doi":"10.7554/elife.59659","title":"Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis","abstract":"Bone remodeling involves a balance between bone resorption and formation. The mechanisms underlying bone remodeling are not well understood. DEF6 is recently identified as a novel loci associated with bone mineral density. However, it is unclear how Def6 impacts bone remodeling. We identify Def6 as a novel osteoblastic regulator that suppresses osteoblastogenesis and bone formation. Def6 deficiency enhances both bone resorption and osteogenesis. The enhanced bone resorption in Def6 -/- mice dominates, leading to osteoporosis. Mechanistically, Def6 inhibits the differentiation of both osteoclasts and osteoblasts via a common mechanism through endogenous type-I IFN-mediated feedback inhibition. RNAseq analysis shows expression of a group of IFN stimulated genes (ISGs) during osteoblastogenesis. Furthermore, we found that Def6 is a key upstream regulator of IFNβ and ISG expression in osteoblasts. Collectively, our results identify a novel immunoregulatory function of Def6 in bone remodeling, and shed insights into the interaction between immune system and bone.","journal":"eLife","year":2020,"id":102004,"datarank":1.0407834287881368,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.5409527522618562,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.5409527522618562,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":20,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.s1rn8pk53"],"GEO":["GSE148455"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":499971,"name":"Courtney Ng","orcid":null,"position":1,"is_corresponding":false},{"id":463633,"name":"Kazuki Inoue","orcid":"0000-0001-6305-9374","position":2,"is_corresponding":false},{"id":498880,"name":"Ziyu Chen","orcid":"0000-0001-5562-7554","position":3,"is_corresponding":false},{"id":498881,"name":"Yuhan Xia","orcid":"0000-0003-1862-6135","position":4,"is_corresponding":false},{"id":334720,"name":"Xiaoyu Hu","orcid":"0000-0002-4289-6998","position":5,"is_corresponding":false},{"id":106894,"name":"Matthew B. Greenblatt","orcid":"0000-0001-9794-8532","position":6,"is_corresponding":false},{"id":420518,"name":"Alessandra B. Pernis","orcid":"0000-0001-8259-1446","position":7,"is_corresponding":false},{"id":339282,"name":"Baohong Zhao","orcid":"0000-0002-1286-0919","position":8,"is_corresponding":false},{"id":498879,"name":"Zhonghao Deng","orcid":"0000-0002-0857-010X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T22:40:51.552773Z","pmid":"33373293","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":[]}