PurposeSclerostin, an inhibitor of Wnt/β-catenin signaling, exerts negative effects on bone formation and contributes to periodontitis-induced alveolar bone loss. Recent studies have demonstrated that serum sclerostin levels are increased in diabetic patients and that sclerostin expression in alveolar bone is enhanced in a diabetic periodontitis model. However, the molecular mechanism of how sclerostin expression is enhanced in diabetic patients remains elusive. Therefore, in this study, the effect of hyperglycemia on the expression of sclerostin in osteoblast lineage cells was examined.MethodsC2C12 and MLO-Y4 cells were used in this study. In order to examine the effect of hyperglycemia, the glucose concentration in the culture medium was adjusted to a range of levels between 40 and 100 mM. Gene expression levels were examined by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Top-Flash reporter was used to examine the transcriptional activity of the β-catenin/lymphoid enhanced factor/T-cell factor complex. Tumor necrosis factor-alpha (TNFα) protein levels were examined with the enzyme-linked immunosorbent assay. The effect of reactive oxygen species on sclerostin expression was examined by treating cells with 1 mM H2O2 or 20 mM N-acetylcysteine.ResultsThe high glucose treatment increased the mRNA and protein levels of sclerostin. High glucose suppressed Wnt3a-induced Top-Flash reporter activity and the expression levels of osteoblast marker genes. High glucose increased reactive oxygen species production and TNFα expression levels. Treatment of cells with H2O2 also enhanced the expression levels of TNFα and sclerostin. In addition, N-acetylcysteine treatment or knockdown of TNFα attenuated high glucose-induced sclerostin expression.ConclusionsThese results suggest that hyperglycemia increases sclerostin expression via the enhanced production of reactive oxygen species and TNFα.Graphical Abstract

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.

Background/Aims: Chronic hepatitis C virus (HCV) infections put patients at risk of serious liver disease and adversely affects patient quality of life (QoL). MOSAIC (International Multicenter Prospective Observational Study to Evaluate the Epidemiology, Humanistic and Economic Outcomes of Treatment for Chronic Hepatitis C Virus) was a prospective, noninterventional, international, multicenter study that aimed to describe the epidemiology of the infection, the impact of the infection on health-related QoL (HRQoL) and daily activities, and healthcare resource use related to HCV and treatment. Here, we present the results on HRQoL and daily activity impairment in consecutively enrolled South Korean patients treated with interferon (IFN)-containing regimens prospectively followed for up to 48 weeks. Methods: General HRQoL, HCV-specific HRQoL, perceived health state, and work/ general activity impairments were measured using the Eu-roQoL 5-dimension 5-level (EQ-5D-5L), HCV patient-reported outcomes (HCV-PRO), EQ-5D Visual Analog Scale, and Work Productivity and Activity Impairment questionnaires, respectively. Results: Thirty-three of the 100 enrolled patients initiated IFN-based treatment, with an intended duration of 24 weeks for 20 patients and 48 weeks for 12 patients; this information was missing for one patient. Fourteen patients (42.4%) prematurely withdrew. After treatment initiation, IFNtreated patients showed a trend towards deterioration of both general (baseline: 0.87±0.103, week 4: 0.77±0.153) and HCV-specific (baseline: 76.2±19.5, week 4: 68.2±22.3) HRQoL. The scores recovered somewhat towards the end of treatment (EOT) (0.84±0.146 for EQ-5D-5L and 70.8±21.9 for HCV-PRO). The perceived health state and work/general activity impairment displayed similar temporal patterns. Conclusions: Initiating IFN-based treatment prompted some deterioration in general and HCV-related HRQoL, accompanied by impaired daily activities and most work productivity measures; however, the HRQoL and productivity scores improved towards the EOT. HRQoL impairment upon treatment initiation likely contributed to treatment discontinuation.

Erratum

We aimed to evaluate the safety and effectiveness of darunavir (DRV) in the treatment of human immunodeficiency virus-1 (HIV-1) infection in Korea. From October 29, 2010, 225 eligible patients with HIV-1 infection receiving DRV were enrolled. DRV was administered with other antiretroviral agents, and followed for 24 weeks. The primary objective was safety evaluation, and effectiveness was assessed by viral load and CD4 T cell counts after 12 weeks and 24 weeks. Adverse drug reactions occurred in 18 patients (9.2%); diarrhea was the most common. Viral load was controlled (<400 copies/mL) in 90.9% of patients. CD4 T cell counts were increased 45.0/mm 3 significantly at Week 12 ( P = 0.0002), and 70.5/mm 3 at Week 24 ( P <0.0001). DRV safety and effectiveness was consistent with previous studies.