Interleukin-32 Gamma Stimulates Bone Formation by Increasing miR-29a in Osteoblastic Cells and Prevents the Development of Osteoporosis

• Published in: Scientific reports Vol. 7; no. 1; p. 40240
• Main Authors: Lee, Eun-Jin, Kim, Sang-Min, Choi, Bongkun, Kim, Eun-Young, Chung, Yeon-Ho, Lee, Eun-Ju, Yoo, Bin, Lee, Chang-Keun, Hong, Seokchan, Kim, Beom-Jun, Koh, Jung-Min, Kim, Soo-Hyun, Kim, Yong-Gil, Chang, Eun-Ju
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 12.01.2017
• Subjects: Animals; Bone Density; Bone growth; Bone loss; Bone mineral density; Bone Remodeling; Bone turnover; Cytokines; Dkk1 protein; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Interleukins - blood; Interleukins - metabolism; Mice, Transgenic; MicroRNAs - metabolism; Osteoblasts; Osteoblasts - metabolism; Osteogenesis; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - prevention & control; Ovariectomy; Rheumatic diseases; Rodents; Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep40240

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.