title: Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.
abstract: The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: An
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Department of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510140, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, Shaanxi 710032, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, Shaanxi 710032, China.
authors.forename: Qintao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D060833:Cellular Microenvironment; D002908:Chronic Disease; D059865:Endoplasmic Reticulum Stress; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000473:pathology; D010518:Periodontitis / Q000150:complications* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051548:Histone Acetyltransferases; D019892:eIF-2 Kinase; C487137:KAT6B protein, human