the effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts促炎细胞因子肿瘤坏死因子-α的影响对人体关节囊myofibroblasts.pdfVIP

Mattyasovszky et al: Arthritis Research Therapy 2010, 12:R4 /content/12/1/R4 R E S E A R C H A R T I C L E Open Access Research article The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts †1 †1 2 1 1 Stefan G Mattyasovszky* , Alexander Hofmann , Christoph Brochhausen , Ulrike Ritz , Sebastian Kuhn , 1 3 1 4 1 Jochen Wollstädter , Hendrik Schulze-Koops , Lars P Müller , Bernhard Watzer and Pol M Rommens Abstract Introduction: Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown. Methods: In this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) on cellular functions of human joint capsule MFs. MFs were challenged with different concentrations of TNF-α with or without both its specifically inactivating antibody infliximab (IFX) and cyclooxygenase-2 (COX2) inhibitor diclofenac. Cell proliferation, gene expression of both alpha-smooth muscle actin (α-SMA) and collagen type I, the synthesis of prostaglandin derivates E2, F1A, and F2A, as well as the ability to contract the extracellular matrix were assayed in monolayers and in a