ISG15 is involved in chondrogenic differentiation through activation of IFN-γ signaling.

Interferon-gamma (IFN-γ) was found to increase in the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). However, few studies have been conducted to elucidate the role of IFN-γ in cartilage metabolism and regeneration. In this study, we investigated whether cartilage regeneration is driven by interferon-stimulated gene 15 (ISG15) under the control of IFN-γ.

Interferon-gamma signaling promotes cartilage regeneration after injury.

Osteoarthritis is a common chronic disease and major cause of disability and chronic pain in ageing populations. In this pathology, the entire joint is involved, and the regeneration of articular cartilage still remains one of the main challenges. Here, we investigated the molecular mechanisms underlying cartilage regeneration in young mice using a full-thickness cartilage injury (FTCI) model.

A causative role for periarticular skeletal muscle weakness in the progression of joint damage and pain in OA.

Although osteoarthritis (OA) is regarded as a disease of the articular cartilage, recent research has demonstrated alterations in periarticular muscles that surround the affected joint. Here, we investigated changes in periarticular muscle during the progression of OA, as well as the cause-and-effect relationship between muscle weakness and OA, in a mouse model of OA by destabilization of the medial meniscus (DMM). Pathological phenotypes in the periarticular muscles were assessed in the early and late stages of OA by DMM.

Correlation between the ratio of physician consultation fees to hourly minimum wage and consultation length: a cross-sectional study of nine countries.

Objectives: Current healthcare reimbursement system is criticised for not adequately compensating physicians' cognitive services. This study was performed to examine primary care physicians' consultation fees in nine countries, relative to the national hourly minimum wage and to examine the correlations of the physician consultation fee with consultation length and other healthcare indices.

Design And Outcome Measures: Nine reference countries for which healthcare statistics are publicly available and outpatient consultation is compensated by fee-for-service payment were selected.

Trends in hospital visits and healthcare costs of gout and seropositive rheumatoid arthritis in Korea from 2010 to 2017 using National Healthcare Claims.

Background/aims: We examined temporal trends in the rate of gout and seropositive rheumatoid arthritis (RA) hospital visits and healthcare costs in Korea.

Methods: We conducted a serial cross-sectional analysis of Korean national healthcare claims. We calculated the annual increase in hospital visits (emergency department [ED] visits, outpatient visits, and hospitalizations) and total healthcare costs per visit.

Molecular Mechanisms of Sex-Related Differences in Arthritis and Associated Pain.

Clinical conditions leading to chronic pain show important sex-related differences in the prevalence, severity, and degree of functional disability. Decades of epidemiological and clinical studies have demonstrated that women are more sensitive to pain than men. Arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is much more prevalent in females and accounts for the majority of pain arising from musculoskeletal conditions.

Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.

Osteoarthritis (OA) is the most prevalent joint disease in older people and is characterized by the progressive destruction of articular cartilage, synovial inflammation, changes in subchondral bone and peri-articular muscle, and pain. Because our understanding of the aetiopathogenesis of OA remains incomplete, we haven't discovered a cure for OA yet. This review appraises novel therapeutics based on recent progress in our understanding of the molecular pathogenesis of OA, including pro-inflammatory and pro-catabolic mediators and the relevant signalling mechanisms.

Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency.

When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic 'scaling' of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.

The transcription factor Foxf1 binds to serum response factor and myocardin to regulate gene transcription in visceral smooth muscle cells.

Smooth muscle cells (SMCs) modulate their phenotype from a quiescent contractile state to a dedifferentiated, proliferative and migratory state during the pathogenesis of many diseases, including intestinal pseudoobstruction. Understanding how smooth muscle gene expression is regulated in these different phenotypic states is critical for unraveling the pathogenesis of these diseases. In the current study we examined the specific roles of Foxf1 in visceral SMC differentiation.

The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia.

Objective: The proliferation and remodeling of vascular smooth muscle cells (VSMCs) is an important pathological event in atherosclerosis and restenosis. Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat (in Flightless 1) interacting protein-1].

Methods And Results: MicroRNA microarray revealed that miR-132 was upregulated in the rat carotid artery after catheter injury, which was further confirmed by quantitative real-time RT-PCR.

Enhancer of polycomb1 lessens neointima formation by potentiation of myocardin-induced smooth muscle differentiation.

Objective: Previously, we reported that enhancer of polycomb1 (Epc1) induces skeletal muscle differentiation through the serum response factor (SRF). Considering that SRF plays a critical role in vascular smooth muscle cell (VSMC) differentiation, we expected that Epc1 also works in VSMCs. Here we examined the effect of Epc1 on neointima formation after arterial balloon injury and the underlying mechanism.

SWI/SNF complexes containing Brahma or Brahma-related gene 1 play distinct roles in smooth muscle development.

SWI/SNF ATP-dependent chromatin-remodeling complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) play important roles in mammalian development. In this study we examined the roles of Brg1 and Brm in smooth muscle development, in vivo, through generation and analysis of mice harboring a smooth muscle-specific knockout of Brg1 on wild-type and Brm null backgrounds. Knockout of Brg1 from smooth muscle in Brg1(flox/flox) mice expressing Cre recombinase under the control of the smooth muscle myosin heavy-chain promoter resulted in cardiopulmonary defects, including patent ductus arteriosus, in 30 to 40% of the mice.

Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance.

The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90α and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation.

Histone methyltransferase PRDM8 regulates mouse testis steroidogenesis.

A family of PRDM proteins are similar to histone methyltransferases (HMTases) with SET domain in that they modulate different cellular processes, including transcriptional regulation, through chromatin modifying activities. By applying a bioinformatic approach, we searched for proteins containing the SET domain and identified a double zinc-finger domain containing PRDM8 with HMTase activity. In vitro HMTase assay and immunoblot analysis revealed that PRDM8 specifically methylates H3K9 of histones which indicates transcriptional repression activity of PRDM8.

Enhancer of polycomb1 acts on serum response factor to regulate skeletal muscle differentiation.

Skeletal muscle differentiation is well regulated by a series of transcription factors. We reported previously that enhancer of polycomb1 (Epc1), a chromatin protein, can modulate skeletal muscle differentiation, although the mechanisms of this action have yet to be defined. Here we report that Epc1 recruits both serum response factor (SRF) and p300 to induce skeletal muscle differentiation.

Activation of histone deacetylase 2 by inducible heat shock protein 70 in cardiac hypertrophy.

Diverse cardiac diseases induce cardiac hypertrophy, which leads to dilatation and heart failure. We previously reported that hypertrophy can be blocked by class I histone deacetylase (HDAC) inhibitor, which prompted us to investigate the regulatory mechanism of class I HDACs. Cardiac hypertrophy was introduced by aortic banding, by infusion of isoproterenol or angiotensin II, or by swimming.

Nrf2-mediated induction of detoxifying enzymes by alantolactone present in Inula helenium.

Our previous study showed that a methanol extract of Inula helenium had the potential to induce detoxifying enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) activity. In this study the methanol extract was further fractionated using silica gel chromatography and vacuum liquid chromatography, to yield pure compounds alantolactone and isoalantolactone as QR inducers. Alantolactone caused a dose-dependent induction of antioxidant enzymes including QR, GST, gamma-glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse hepatoma cells.

Effect of 5-O-Methylhirsutanonol on nuclear factor-kappaB-dependent production of NO and expression of iNOS in lipopolysaccharide-induced RAW264.7 cells.

Diarylheptanoids are known to have anti-inflammatory and anti-atherosclerotic activities in various cell types, including macrophages. 5- O-Methylhirsutanonol (5-MH) isolated from the leaves of Alnus japonica Steud exhibited the antioxidant activities on Cu (2+)- and AAPH-mediated low-density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. In the main study, we examined anti-inflammatory activities of 5- O-methylhirsutanonol (5-MH) on nuclear factor kappaB (NF-kappaB)-dependent nitric oxide (NO) production and expression of inducible nitric oxide synthease (iNOS) in lipopolysaccharide (LPS)-induced RAW264.

Effects of diarylheptanoids on the tumor necrosis factor-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.

Atherosclerosis is a chronic inflammatory disease that is characterized by infiltration of mononuclear lymphocytes into the intima through the expression of adhesion molecules on the arterial wall. In the present study, we report the inhibitory effects of two diarylheptanoids, 5-O-methylhirsutanonol (1) and oregonin (2), isolated from the methanolic extracts of Alnus japonica leaves, on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). Compounds 1 and 2 inhibited tumor necrosis factor (TNF)-alpha-induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which also prevented adhesion of monocytes to HUVECs, and slightly suppressed the mRNA expression of the inflammation-associated gene interleukin-1beta (IL-1beta).

Induction of detoxifying enzyme by sesquiterpenes present in Inula helenium.

Our previous study showed that the methanolic extract of Inula helenium (elecampane) had the potential to induce detoxifying enzymes such as quinine reductase (QR) and glutathione S-transferase. In this study we further fractionated the methanolic extract into hexane-, dichloromethane-, butanol-, and water-soluble fractions according to polarity. The hexane fraction showed the highest QR-inducing activity and also induced glutathione S-transferase in a dose-dependent manner.

Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation.

Homeodomain only protein, Hop, is an unusual small protein that modulates target gene transcription without direct binding to DNA. Here we show that Hop interacts with Enhancer of Polycomb1 (Epc1), a homolog of a Drosophila polycomb group gene product that regulates transcription, to induce the skeletal muscle differentiation. Yeast two-hybrid assay with the human adult heart cDNA library revealed that Hop can associate with Epc1.

Antioxidant activities of abietane diterpenoids isolated from Torreya nucifera leaves.

Investigation on antioxidant compounds from the ethanolic extracts of Torreya nucifera leaves resulted in the isolation of abietane diterpenoids, a known 18-methylesterferruginol (1) and a new 18-dimethoxyferruginol (2). The structures of compounds 1 and 2 were elucidated on the basis of their spectroscopic analyses. Compounds 1 and 2 inhibited the Cu2+-mediated, 2,2'-azobis(2-amidinopropane)hydrochloride-mediated and 3-morpholinosydnonimine-1-mediated low-density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substances assay as well as the macrophage-mediated LDL oxidation.

Phellinsin A from Phellinus sp. PL3 exhibits antioxidant activities.

Phellinsin A, which was isolated from the culture broth of Phellinus sp. PL3, exhibited significant low-density lipoproteins (LDL)-antioxidant activity. It inhibited the Cu2+-mediated oxidation of LDL (IC50: 5.

Antioxidant effects of diarylheptanoid derivatives from Alnus japonica on human LDL oxidation.

Two diarylheptanoids, oregonin (1) and hirsutanone (2), were isolated by bioassay-guided fractionation of the methanol extracts of the leaves of Alnus japonica Steud and their structures were elucidated from their spectroscopic data. Compounds 1 and 2 exhibited significant low-density lipoprotein (LDL)-antioxidant activities, e. g.

Antioxidant activities of a new lignan and a neolignan from Saururus chinensis.

A new diarylbutane lignan, 2'-hydroxy dihydroguaiaretic acid (4), and a known 8-O-4'-type neolignan, machilin D (5), were isolated from the ethyl acetate extracts of the underground parts of Saururus chinensis. Compounds 4 and 5 exhibited low-density lipoprotein (LDL)-antioxidant activity in the thiobarbituric acid-reactive substances (TBARS) assay (4: IC(50)=3.3 microM and 5: IC(50)=3.