%0 Journal Article
%T TGF-¦Â inhibits IL-1¦Â-activated PAR-2 expression through multiple pathways in human primary synovial cells
%A Shin-Han Tsai
%A Ming-Thau Sheu
%A Yu-Chih Liang
%A Hsiu-Tan Cheng
%A Sheng-Shiung Fang
%A Chien-Ho Chen
%J Journal of Biomedical Science
%D 2009
%I BioMed Central
%R 10.1186/1423-0127-16-97
%X Osteoarthritis (OA) is a degenerative disease characterized by depletion of articular cartilage and formation of osteophytes [1]. OA formed under the condition of imbalance between anabolic and catabolic mediators, when catabolism is greater than anabolism, the risk of OA raises. The catabolic mediators include MMPs, ADAMTS, ADAM, IL-1¦Â, IL-17, IL-18 and TNF-¦Á, which increase degradation of cartilage and inhibit synthesis of metalloproteinase inhibitors such as TIMPs, tenascin and YKL-40. The anabolic mediators include TGF-¦Â, IGF-1, FGFs and BMPs, which stimulate synthesis and repairing of cartilage. The secreted proinflammatory cytokines and metalloproteinases up-regulate expression of chondrocyte PAR-2, stimulating more secretion of proinflammatory cytokines and metalloproteinases to enhance inflammatory response [2,3] and degradation of ECM components of cartilage tissue, causing progressive loss of cartilage. Furthermore, fragments of protein degradation, like fibronectin fragments and collagen type II fragments, seem to play a role in inducing degradation of cartilage [4,5] as well as stimulating chondrocytes to repair the matrix.TGF-¦Â, a prominent member of the TGF-¦Â superfamily of ligands which include TGF-¦Â s and BMPs, is vital for the homeostasis of numerous cellular functions, including cell growth, differentiation, and apoptosis in a broad spectrum of tissues [6]. TGF-¦Â signals are propagated through direct physical interactions with the extracellular domain of essentially two transmembrane serine/threonine kinase receptors (T¦Â-RI and T¦Â-RII), which transduce a number of secondary signals, most notably Smads 2 and 3 as well as PI3-kinase and various members of the mitogen activated protein kinase (MAPK) family [7-10]. CTGF, a member of CCN family, is a cysteine-rich matricellular protein. Expression of this protein is potently induced by TGF-¦Â via Smad pathway. CTGF promotes chondrocytes proliferation through p38 MAPK and differentiation via p42/p44 MAPK.
%U http://www.jbiomedsci.com/content/16/1/97