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

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 ? (IFN-?) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-? 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-? was administered to the model mice. The effects of exogenous IFN-? 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-?. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-? treated mice compared with mice in the AVN group. Treatment with IFN-? increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-? decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-? could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN.

SUBMITTER: Kim KM

PROVIDER: S-EPMC5790483 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Kim Kyoung Min KM Wagle Sajeev S Moon Young Jae YJ Wang Sung Il SI Park Byung-Hyun BH Jang Kyu Yun KY Kim Jung Ryul JR

Oncotarget 20171216 3

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 spe ...[more]

PMID: 29423066

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Project description:BackgroundSilent information regulator 2 (SIR2) proteins are a family of NAD + -dependent protein deacetylases that are considered potential targets for anti-parasitic agents. In this study, we cloned and characterized SIR2A of the protozoan parasite Eimeria tenella (EtSIR2A) and investigated its protective efficacy as a DNA vaccine.MethodsThe EtSIR2A gene encoding 33.37 kDa protein from E. tenella second-generation merozoites was cloned, and recombinant EtSIR2A protein (rEtSIR2A) was produced in an Escherichia coli expression system. The rEtSIR2A was used to immunize rabbits. Anti-rEtSIR2A antibodies were used to determine the immunolocolization of EtSIR2A in the parasite by immunofluorescence assay (IFA). Transcript and protein expression of EtSIR2A in different development stages of E. tenella were observed by quantitative real-time PCR (qPCR) and western blot (WB) analysis, respectively. The recombinant plasmid pCAGGS-EtSIR2A was constructed and its efficacy against E. tenella infection in chickens was evaluated.ResultsqPCR and WB analysis revealed EtSIR2A expression was developmentally regulated at both the mRNA and protein levels. EtSIR2A mRNA levels were higher in unsporulated oocysts than at other developmental stages, including sporulated oocysts, sporozoites and second-generation merozoites. In contrast, EtSIR2A protein expression levels were highest in second-generation merozoites, moderate in unsporulated oocysts and sporulated oocysts and lowest in sporozoites. Immunostaining with anti-rEtSIR2A antibody indicated that EtSIR2A was mainly located in the cytoplasm of sporozoites and second-generation merozoites, and was strongly expressed during first stage schizogony. Animal-challenge experiments demonstrated that immunization with pCAGGS-EtSIR2A significantly increased average body-weight gain, and decreased mean lesion score and oocyst output in chickens.ConclusionsThese results suggest that EtSIR2A may play an important role in parasite cell survival and may be an effective candidate for the development of new vaccines against E. tenella infection in chickens.

Project description:BACKGROUND:Osteonecrosis of the femoral head (ONFH) is a frequent orthopedic disease leading to destruction of the hip joint and disabling arthritis. Several procedures have been developed to treat the joint deterioration in case of osteonecrosis, trying to avoid or delay an intervention of total hip replacement, especially in young patients. The aim of this study was to analyze the use of autologous bone micrografts derived from cancellous bone in the management of avascular ONFH. The treatment described was implemented using the Rigenera® protocol to obtain autologous micrografts: small fragments of cancellous bone collected by femoral neck, disaggregated and injected in the necrotic area using an empty screw. MATERIALS AND METHODS:Twenty adult patients affected by avascular ONFH were enrolled in this study; all patients reported a preoperative intermittent coxo-arthrosis and limited function of intra and extra rotation of the hip. Inclusion criteria were an Oxford Hip Score between (OHS) 20 and 39, a Harris hip score (HHS) showing pre-operative poor results (lower than 70 points) and a stage II-IIIA and IIIB according with the classification proposed by the Association Research Circulation Osseous (ARCO). RESULTS:Using an MRI evaluation, after six months, the authors observed a complete regression of necrotic area and the restoration of osseous structure. Clinical outcome has been evaluated at 6-12 and 24 months follow-up. At the final F.U. the HHS rised from poor to good results (mean value at final F.U of 84) while the OHS improved significantly already after 21 days from micrografts injection (mean 35.4 ± 7.5) with an increasing trend until to two-year final FU (mean 37.4 ± 9.5). The full recovery of daily and mild sport activities was reached after 20 and 90 days from intervention, respectively. CONCLUSION:The results of this study are suggestive for a new approach in the treatment of avascular ONFH assuming a process of bone regeneration based on a dual mechanism of action, biological and mechanical, induced by micrografts and injected using an empty screw as vehicle.

Dataset Information

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

Publications

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

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