ABSTRACT
Objective To investigate the effects of inflammatory factors TNF-α, IL-1β, IL-6 on expression of mechano growth factor (MGF). Methods In the experimental group, TNF-α and IL-6 at concentration of 25, 50, 100 ng/mL, or IL-1β at concentration of 2.5, 5.0, 10 ng/mL were applied to fibroblast-like synoviocytes (FLSs) for 12 hours. The inhibitor groups were pretreated with PKA pathway inhibitor KT5720 at concentration of 1.0 mmol for 1 hour. The control group remained under the same culture condition as the experimental group, but without any growth factor. Real-time PCR was used to measure the gene expression of MGF. Results Treated with TNF-α at concentration of 25 ng/mL and IL-1β at concentration of 10 ng/mL, the MGF expression in FLSs was significantly increased (P＜0.05). IL-6 had no effect on MGF expression. A specific inhibitor of cAMP-dependent protein kinase, at concentration of 1.0 mmol significantly decreased the activation of MGF synthesis by TNF-α and IL-1β in FLSs (P＜0.05). Conclusions TNF-α at concentration of 25 ng/mL and IL-1β at concentration of 10 ng/mL significantly induce the MGF expression in FLSs, which activate MGF synthesis via the PKA pathway. This study is of significance in improving the application of MGF used in tissue repair area to make up the insufficient stress stimulation.
ABSTRACT
Objective To explore the role of mechanical stimulation in synovium under different pathological conditions through studying the effects of cyclic mechanical stretch on the expression of bone morphogenetic protein 2 (BMP-2) in rheumatoid arthritis (RA) and osteoarthritis (OA) fibroblast-like synoviocytes (FLS). Method 6% and 0.5 Hz stretch generated by Flex cell 4000 tension systems was applied on normal, RA and OA FLS of human knee joint source under normal and inflammatory conditions for 2 h or 6 h, respectively. Results Cyclic mechanical stretch of 6%, 0.5 Hz had no significant effects on the expression of BMP-2 in normal, RA and OA FLS at 2 h, while in RA FLS it increased significantly at 6 h. Inflammatory cytokines (IL-1β) didn’t influence normal FLS at 2 h, but made BMP-2 mRNA significantly increased at 6 h. IL-1β increased BMP-2 mRNA of RA FLS significantly both at 2 h and 6 h. IL-1β increased BMP-2 mRNA of OA FLS significantly only at 2 h, but had no significant effect at 6 h. The co-effect of IL-1β and cyclic mechanical stretch induced the ascension of BMP-2 expression significantly in normal and RA FLS at 2 h, and in normal, RA and OA FLS at 6 h. Conclusions Response of BMP-2 mRNA to mechanic stimulation and IL-1β in normal, RA and OA FLS were different. Inflammation may play a more important role than mechanical stimulation in the pathogenesis of RA and OA. Synergetic effect in inflammation and mechanical stimulation were found in OA FLS at 6 h, which reveals that they may co-act in the occurrence and development of OA.
ABSTRACT
Tumor metastasis, the main biological characteristic of malignance tumor, is the important cause of death for most cancer patients. The process of tumor metastasis is complex and involves a dynamic combination of vessel, lymphatic system and microenvironment of metastatic organ. Organ specific arrest and adhesion of tumor cells within microvessels of potential target organs is a vital step during the formation of blood borne metastasis. In this article, recent studies on the organ specific arrest and adhesion of circulating tumor cells were comprehensively summarized focusing on the related theory, hypothesis and methodology including the model employed and the research methods involved. The article also discussed the biomechanical factors, endothelial cells and chemokines regulating the arrest and adhesion of circulating tumor cells, and pointed out some recent new phenomena as well as new approaches and directions worthy of investigation.