{"doi":"10.1101/2021.12.14.472623","title":"Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis","abstract":"Abstract Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur. In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement a ligature around the upper second molar which leads to inflammation and bone breakdown and faithfully replicates the bacterially-induced inflammatory etiology of human PD to induce bone degeneration. After 10 days, the ligature is removed and the mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and the regenerative response is completely blocked by siHIF1a . Here, we observe that timed-release 1,4-DPCA rapidly and completely restores bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to stem cell migration into the site and/or de-differentiation of local tissue, PDL cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222154,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458469,"name":"Tetsuhiro Kajikawa","orcid":"0000-0001-8416-9126","position":1,"is_corresponding":false},{"id":823294,"name":"Kamila Bedelbaeva","orcid":null,"position":2,"is_corresponding":false},{"id":823295,"name":"Azamat Aslanukov","orcid":null,"position":3,"is_corresponding":false},{"id":823296,"name":"Sam Bollinger","orcid":null,"position":4,"is_corresponding":false},{"id":628482,"name":"Yong Zhang","orcid":"0000-0003-0513-8941","position":5,"is_corresponding":false},{"id":823297,"name":"David Sarfatti","orcid":null,"position":6,"is_corresponding":false},{"id":254060,"name":"Jing Cheng","orcid":"0000-0002-5379-2203","position":7,"is_corresponding":false},{"id":245083,"name":"Phillip B. Messersmith","orcid":"0000-0002-1197-333X","position":8,"is_corresponding":false},{"id":41941,"name":"George Hajishengallis","orcid":"0000-0001-7392-8852","position":9,"is_corresponding":false},{"id":669415,"name":"Ellen Heber‐Katz","orcid":"0000-0002-2987-9034","position":10,"is_corresponding":false},{"id":823293,"name":"Elan Zebrowitz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","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":[]}