Background/AimsSKI306X, 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.MethodsHuman 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.ResultsSKI306X 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.ConclusionsSKI306X 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.
Whipple's disease (WD) is a chronic infectious disorder of multi-system caused by Tropheryma whippelii (TW). Although the prominent symptoms are diarrhea, malabsorption, and weight loss, the arthritis may precede the gastrointestinal symptoms [1]. Furthermore, some cases of WD shows the clinical manifestations of spondyloarthropathy (SpA), such as oligoarthritis pattern, axial involvement, sacroiliitis, and association with HLA-B27 [2].The presence of periodic acid-SchiV-staining foamy macrophages in the lamina propria of duodenum is diagnostic of WD [1]. Recently the molecular diagnosis using TW-speciWc gene ampliWcation is promising. The sequencing of 23S ribosomal RNA (rRNA) gene was established and it provided a basis for molecular diagnosis in the absence of reliable culture and serology [3].As an eVort to disclose whether TW is associated with the pathogenesis of SpA, we investigated the prevalence of TW DNA in saliva of patients with SpA and in healthy controls.A total of 108 patients who were diagnosed as ankylosing spondylitis were enrolled. As a control group, we recruited 132 healthy volunteers. There were no diVerences seen in age distribution and sex between the cases and the controls.Participants were asked to rinse the mouth with tap water to remove any remaining food. Approximately 5 ml of whole saliva was collected by having subjects spit into 50 ml sterile collection tubes. The salivary samples were stored at ¡70°C until DNA was extracted.All DNA samples had been tested using semi-nested PCR for hypervariable region of domain III of the 23S rDNA with primers HGC-23InsF and TW-23InsR1 and for nested re-ampliWcation TW-23InsF and TW23InsR2 were used [3].We found two cases and two controls to be PCR-positive in the saliva. This leads to prevalence rates of 1.5% (95% CI 2.0-7.6%) in controls and 1.9% (95% CI 4.0-11.3%) in cases. In contrary to previous western reports [4,5], the prevalence value of TW DNA in Korean patients without WD is signiWcantly low. This may explain that there is so far no any reported case of WD in Korea. All specimens which PCR was positive were analyzed by direct sequencing in order to conWrm. They were identical to the searched sequence for TW (http://www.ncbi.nlm. nih.gov/entrez/query.fcgi?db=Nucleotide).The previous study showed that all PCR results for 16S rRNA were negative in patients with unexplained seronegative oligoarthritis or polyarthritis, and TW does not seem to be frequently involved in this clinical setting [6].
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.
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