title: Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages.
abstract: Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in peritoneal macrophages isolated from DIO mice when challenged with Porphyromonas gingivalis LPS (pg.lps). To elucidate the interaction of APN and JMJD3 involved in macrophage transformation in the context of inflammation, we designed the loss and gain-function experiments of APN in vivo with APN(-/-) mice with experimental periodontitis and in vitro with macrophage isolated from APN(-/-) mice. For the first time, we found that APN can help to reduce periodontitis-related bone loss, modulate JMJD3 and IRF4 expression, and macrophage infiltration. Therefore, it can be inferred that APN may contribute to anti-inflammation macrophage polarization by regulating JMJD3 expression, which provides a basis for macrophage-centered epigenetic therapeutic strategies.
authors.affiliation: Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, China.|Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Dongying
authors.initials: D
authors.lastname: Xuan
authors.affiliation: Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, China.|Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Liming
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Dana
authors.initials: D
authors.lastname: Murry
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Tianchi
authors.initials: T
authors.lastname: Tu
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Yin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.affiliation: Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.affiliation: Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts.
authors.forename: Paloma
authors.initials: P
authors.lastname: Valverde
authors.affiliation: Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jincai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors.forename: Jake
authors.initials: J
authors.lastname: Chen
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D044127:Epigenesis, Genetic; D007113:Immunity, Innate; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D016328:NF-kappa B / Q000378:metabolism; D010518:Periodontitis / Q000235:genetics* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation; D000099218:Interferon Regulatory Factor-4
chemical_list: D052242:Adiponectin; D050835:Interferon Regulatory Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000099218:Interferon Regulatory Factor-4; C523761:Kdm6b protein, mouse