Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation

// Kyoung Min Kim 1, * , Sajeev Wagle 2, * , Young Jae Moon 3 , Sung Il Wang 2 , Byung-Hyun Park 3 , Kyu Yun Jang 1 and Jung Ryul Kim 2 1 Department of Pathology, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University–Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54896, Republic of Korea 2 Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University–Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54896, Republic of Korea 3 Department of Biochemistry, Chonbuk National University Medical School, Research Institute for Endocrine Sciences, Jeonju 54896, Republic of Korea * These authors contributed equally to this work Correspondence to: Jung Ryul Kim, email: jrkeem@jbnu.ac.kr Kyu Yun Jang, email: kyjang@jbnu.ac.kr Keywords: ischemic osteonecrosis; interferon-β; silent information regulator transcript-1; interleukin 6; osteoclast Received: June 09, 2017      Accepted: November 26, 2017      Published: December 16, 2017 ABSTRACT Synovitis of the affected joint is a common in avascular osteonecrosis (AVN). Increased levels of pro-inflammatory cytokine interleukin-6 (IL-6) have been reported in AVN, but the mechanism of this increase remains unclear. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, inhibits the release of inflammatory cytokines. Interferon β (IFN-β) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-β treatment on AVN and to evaluate the specific signal pathway relating to IL-6 and SIRT1 affected during AVN. Using a dissection microscope, AVN was surgically induced in the distal femurs of mice. Exogenous IFN-β was administered to the model mice. The effects of exogenous IFN-β on AVN model mice were assessed using hematoxylin eosin and safranin-O staining, and bone resorption activity was measured using tartrate-resistant acid phosphatase (TRAP) and CD68 staining. Western blots, real-time RT-PCR, and immunohistochemical staining were performed to evaluate the production of SIRT1 and IL-6 in tissues. The RAW 264.7 cell line and bone marrow derived osteoclasts treated with exogenous IFN-β. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-β treated mice compared with mice in the AVN group. Treatment with IFN-β increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-β decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-β could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN.