title: Interleukin-32 Gamma Stimulates Bone Formation by Increasing miR-29a in Osteoblastic Cells and Prevents the Development of Osteoporosis.
abstract: Interleukin-32 gamma (IL-32γ) is a recently discovered cytokine that is elevated in inflamed tissues and contributes to pathogenic features of bone in human inflammatory rheumatic diseases. Nevertheless, the role of IL-32γ and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32γ in bone remodeling and the hypothetical correlation between IL-32γ and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32γ showed reduced bone loss with advancing age, increased bone formation, and high osteogenic capacity of osteoblast compared to wild-type (WT) mice through the upregulation of miR-29a, which caused a reduction of Dickkopf-1 (DKK1) expression. IL-32γ TG mice were protected against ovariectomy (OVX)induced osteoporosis compared with WT mice. Decreased plasma IL-32γ levels were associated with bone mineral density (BMD) in human patients linked to increased DKK1 levels. These results indicate that IL-32γ plays a protective role for bone loss, providing clinical evidence of a negative correlation between IL-32γ and DKK1 as bone metabolic markers.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Yoo
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Chang-Keun
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Seokchan
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Beom-Jun
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 05066, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Yong-Gil
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins / Q000097:blood / Q000378:metabolism*; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D010024:Osteoporosis / Q000378:metabolism* / Q000517:prevention & control; D010052:Ovariectomy
chemical_list: C501127:Dkk1 protein, mouse; C496971:IL32 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs