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

ABSTRACT: Interleukin-32 gamma (IL-32?) 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-32? and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32? in bone remodeling and the hypothetical correlation between IL-32? and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32? 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-32? TG mice were protected against ovariectomy (OVX)induced osteoporosis compared with WT mice. Decreased plasma IL-32? levels were associated with bone mineral density (BMD) in human patients linked to increased DKK1 levels. These results indicate that IL-32? plays a protective role for bone loss, providing clinical evidence of a negative correlation between IL-32? and DKK1 as bone metabolic markers.

SUBMITTER: Lee EJ 

PROVIDER: S-EPMC5228062 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature