Crucial role of visfatin/pre–B cell colony‐enhancing factor in matrix degradation and prostaglandin E₂ synthesis in chondrocytes: Possible influence on osteoarthritis

Abstract

Objective. Prostaglandin E 2 (PGE 2 ) is one of the main catabolic factors involved in osteoarthritis (OA), and metalloproteinases (MMPs) are crucial for cartilage degradation. PGE 2 synthesis under inflammatory conditions is catalyzed by cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), whereas NAD؉-dependent 15-hydroxy-PG dehydrogenase (15-PGDH) is the key enzyme implicated in PGE 2 catabolism. The present study was undertaken to investigate the contribution of visfatin, an adipose tissue-derived hormone, to the pathophysiology of OA, by examining its role in PGE 2 synthesis and matrix degradation. Osteoarthritis (OA) causes pain and dysfunction and is the leading cause of disability in elderly people in industrialized countries (1). It results in breakdown of articular cartilage with concomitant changes in the underlying bone, development of osteophytes, and some degree of synovial inflammation (2). The extracellular matrix of cartilage is destroyed and the phenotype of chondrocytes altered due to changes in their pattern of gene expression. They lose their differentiated phenotype and undergo focal cell death and degeneration (3). Several epidemiologic studies have shown a positive

Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

“…Recently, the role of visfatin at joint cartilage and synovial level is going to be enlightened. Indeed, after the initial observation of increased visfatin circulating levels in RA patients by our group (Otero et al 2006), other evidence pointed to a proinflammatory role of visfatin both in chondrocytes and synovial fibroblast (Brentano et al 2007, Gosset et al 2008) suggesting a role for visfatin as a destructive mediator of joint inflammation.…”

Suppression of leukocyte infiltration and cartilage degradation by selective inhibition of pre-B cell colony-enhancing factor/visfatin/nicotinamide phosphoribosyltransferase: Apo866-mediated therapy in human fibroblasts and murine collagen-induced arthrit

“…In this respect, PBEF is abundantly expressed by inflammatory leukocytes and synovial fibroblasts (6,18,31,42,43). Consequently, PBEF may contribute to the regulation of inflammation in joint disease.…”

Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases?

“…The knockout of visfatin/PBEF in these cells resulted in reduced IL-1-mediated PGE 2 release (66). Furthermore, visfatin/PBEF induced the expression and synthesis of matrix-degrading enzymes in murine articular chondrocytes (66). Therefore, MMPs are induced not only by visfatin/PBEF in OASFs but also by chondrocytes themselves, leading to increased cartilage degradation.…”

“…Visfatin/PBEF is produced by different synovial cells within the OA synovium, including chondrocytes, and can be induced by proinflammatory cytokines such as IL-1 (66). Interestingly, in OA chondrocytes, visfatin/ PBEF was also able to trigger prostaglandin E 2 (PGE 2 ) release via increased microsomal PGE synthase 1 synthesis and decreased 15-hydroxyprostaglandin dehydrogenase synthesis.…”