Abstract. osteosarcoma is the most common primary malignancy of the bone. aminopeptidase n (aPn/cD13), a Zn +2 -dependent ectopeptidase localized on the cell surface, is widely considered to influence the invasion mechanism. This study explores the potential involvement of APN in migration and invasion of human osteosarcoma cells in vitro using inhibitors and activators of APN. Cells treated with APN inhibitor bestatin displayed decreased migration and invasion in a Boyden chamber Transwell assay. Western blotting revealed reduced levels of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway proteins, reduced phosphorylation of p38, ERK1/2 and JNK and decreased levels of NF-κB. Bestatin treatment also lowered APN, matrix metalloproteinase (MMP)-2 and -9 enzymatic activity and their mRNA expression. Reduced MMP-2 and -9 protein levels were also observed. By comparison, cells treated with cytokine interleukin-6 (IL-6), a stimulator of APN, displayed increased migration and invasion. Western blotting revealed increased levels of MAPK and PI3K pathway proteins, phosphorylated p38, ERK1/2 and JNK, and NF-κB. IL-6 treatment also increased APN and MMP-2 and -9 enzymatic activity. An increase of APN, MMP-2 and -9 mRNA levels, and MMP-2 and -9 protein levels was also observed. Together these experiments reveal potential enzymatic and signalling roles for aPn in osteosarcoma and establish a starting point for an in-depth analysis of the role of aPn in regulating invasiveness. A deeper knowledge about the regulatory mechanisms of APN may contribute to the development of anti-metastatic therapies.
BackgroundThe aim of this study was to analyze the impact and usefulness of characteristic signal change of a linear black signal on magnetic resonance imaging (MRI) on treatment-related decision making.Material/MethodsForty-one patients with a linear black signal on MRI were enrolled in this prospective study. They were randomly divided into the percutaneous kyphoplasty (PKP) group (n=24) and the conservative treatment group (n=17). Clinical measures, including visual analog scale (VAS) and short-form 36 (SF-36) questionnaire, were analyzed. Radiographic measures, including anterior vertebral body height, kyphosis angle and rate of bone-union, were evaluated.ResultsVAS scores were significantly lower in the PKP group than in the conservative treatment group post-treatment and at one-year follow-up. After one year of treatment, the values for physical functioning, physical health, and body pain were significantly higher in the PKP group than in the conservative treatment group (p<0.05). The PKP group had a significantly higher anterior vertebral body height, rate of bone-union, and lower kyphosis angle than the conservative treatment group at one-year follow-up (p<0.05).ConclusionsIn patients with a linear black signal detected on MRI, the first-choice treatment should be PKP rather than conservative treatment.
The aim of this study was to investigate associations between single nucleotide polymorphisms rs13301537 in asporin (ASPN) and rs373444 in the bone morphogenetic protein 5 (BMP5) gene with knee osteoarthritis (OA) susceptibility in a Chinese Han population. ASPN rs13301537 and BMP5 rs373444 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 510 patients with knee OA and 520 controls were enrolled in the study. CT and CC genotypes of rs13301537, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs13301537 CT heterozygotes compared with TT homozygotes was stronger in females and those aged >65 years. In contrast, the CT and CC genotypes of rs373444 in BMP5 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. Our results showed that ASPN rs13301537 T to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.
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