[Show abstract][Hide abstract] ABSTRACT: Background/Aims
SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-1β-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X.
Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-1β ± oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4.
SKI306X and PV inhibited IL-1β-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-1β-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-1β + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity.
SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.
Preview · Article · Sep 2014 · The Korean Journal of Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT.
Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or imunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM.
We here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.
Full-text · Article · May 2013 · BMC Medical Genomics
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. The dietary flavonoid apigenin has been shown to reduce expression of the myofibroblast phenotype and to inhibit contraction of collagen gels. We investigated the effect of apigenin on the prevention and treatment of a modified bleomycin-induced animal model of scleroderma.
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. An animal model of SSc, the bleomycin-induced mouse model, has been established and used extensively to investigate the pathogenesis of SSc and to seek novel therapeutic agents. We recently developed thermo-reversible combination gels that can be injected subcutaneously and are made in aqueous solution by forming a complex coacervate with the substance of interest and cationic macromolecules, followed by co-formulation with methylcellulose (MC) as a negative thermosensitive polysaccharide. The objective of this study was to demonstrate whether weekly injections of bleomycin using combination gels loaded with bleomycin can induce the skin fibrosis model of SSc in susceptible mouse strains. A low molecular weight MC (4%) gel with 4.5% ammonium sulfate was made in aqueous solution, and mixed with bleomycin. This was injected subcutaneously into female C3H/He mice at weekly intervals. Control mice were injected with the gel made with phosphate-buffered saline. After 4 weeks, histological examination and gene expression assays of cytokines were performed. Examination in vitro showed that more than 80% of the bleomycin was released from the gel by the 4th day. Histological examination showed that dermal thickness increased in the MC-bleomycin-injected group compared with the control, and semi-quantitative analysis indicated that the extent of inflammation did not differ between the groups. In the MC-bleomycin-injected group, dermal fibrosis assessed with the Masson-Trichrome stain and numbers of alpha-smooth muscle actin-positive fibroblastic cells also increased. The procedure for inducing scleroderma in which bleomycin is injected weekly as an easily-made gel system using methylcellulose, can induce dermal fibrosis in susceptible mice without causing inflammation. We believe this system represents a time- saving and convenient procedure that should facilitate research on SSc.
No preview · Article · Mar 2011 · Rheumatology International
[Show abstract][Hide abstract] ABSTRACT: IL-1β is involved in the degradation of articular cartilage in various arthritides, including osteoarthritis (OA). Competitive inhibition of IL-1β by IL-1 receptor antagonists (IL-1Ra) may represent a pathogenesis-based strategy for inhibiting degradation of the cartilage matrix. We investigated the hypothesis that controlled release of IL-1Ra using injectable, thermoreversible and complex coacervate combination gels as drug delivery systems might reduce matrix degradation in OA.
[Show abstract][Hide abstract] ABSTRACT: Objective: Gout is one of the most common forms of inflammatory arthritides among men, which is caused primarily by chronic hyperuricemia. Although pharmacological therapy is the mainstay treatment to manage gout, limiting the consumption of dietary purine is also important. Several epidemiological studies have reported that alcohol consumption is closely related to hyperuricemia and gout. The objective of this study was to determine the purine content in common Korean alcoholic beverages using high performance liquid chromatography (HPLC) to provide a dietary guideline for those with hyperuricemia or gout. Methods: Thirty-five alcoholic beverages were analyzed. Blindly labeled samples of each alcoholic beverage were degassed and frozen. The sample preparation prior to HPLC followed the methods of Japanese researchers. HPLC was performed to analyze adenine, guanine, hypoxanthine, and xanthine content in the alcoholic beverages. Results: The standard curves were linear for all purines. Purine contents were as follows: beer (42.26∼146.39 μmol/L, n=12), medicinal wine (8.2 and 40.41 μmol/L, n=2), rice wine (13.19 μmol/L), Makgeolri (11.71 and 24.72 μmol/L, n=2), red wine (0, 6.03, and 17.9 μmol/L, n=3). No purines were found in fruit wine (n=2), Kaoliang (n=1), white wine (n=1), or distilled alcoholic beverages, such as soju (n=10) or whiskey (n=1).
Full-text · Article · Jan 2010 · The Journal of the Korean Rheumatism Association
[Show abstract][Hide abstract] ABSTRACT: To investigate the genetic association between ankylosing spondylitis (AS) and single nucleotide polymorphisms (SNP) of collagen 6A1 gene (COL6A1), the candidate gene for ossification of the posterior longitudinal ligament.
One-hundred thirty Korean patients with AS (M: 116, F: 14, age: 29.0 +/- 4.6) and 130 age- and sex-matched healthy subjects were recruited. The SNP of G365G, IVS15+39 C/T, IVS21+18 A/C by Snap shot assay and the SNP of IVS32-29T/C, IVS33+15G/A, IVS33+20A/G, and IVS33+55A/G by direct sequencing were genotyped and analyzed. Bonferroni correction was applied to multiple comparisons.
The observed allelic frequencies for these SNP met Hardy-Weinberg equilibrium in all AS and controls. We also found an additional 2 SNP (R783Q and IVS33+88C/T) during direct sequencing. Therefore, a total of 9 SNP were analyzed in this study. There were no significant associations of allelic and genotype variations between AS and controls. The presence of uveitis was marginally associated with a haplotype (CC in G365G + IVS15+39 C/T). The variation of allele or haplotype of COL6A1 is not significantly associated with "more ossified disease."
Because the genetic variations of COL6A1 could not be correlated with the occurrence of AS in Koreans, we conclude that despite common clinical features, AS and ossification of posterior longitudinal ligament are not genetically related, and the hyperostotic condition seen in the 2 diseases might be regulated differently. Further SNP of COL6A1 were not related to radiographic progression of AS. However, we found that the occurrence of uveitis might be related to the genetic variations of COL6A1 in patients with AS.
No preview · Article · Sep 2008 · The Journal of Rheumatology