The potential of adiponectin in driving arthritis.
Articular adipose tissue is a ubiquitous component of human joints, but its local functions are largely unknown. Because recent studies revealed several links between adipose tissue, adipocytokines, and arthritis, we investigated the expression of the adipocytokine adiponectin and its functional role in articular adipose tissue and synovium of patients with different arthritides. In contrast to its protective role in endocrinological and vascular diseases, adiponectin was found to be involved in key pathways of inflammation and matrix degradation in the human joint. The effects of adiponectin in human synovial fibroblasts appear to be highly selective by inducing only two of the main mediators of rheumatoid arthritis pathophysiology, IL-6 and matrix metalloproteinase-1, via the p38 MAPK pathway. Owing to the observation that these effects could be inhibited by different TNF-alpha inhibitors, adipocytokines such as adiponectin may also be key targets for therapeutic strategies in inflammatory joint diseases. In summary, articular adipose tissue and adipocytokines cannot be regarded as innocent bystanders any more in chronic inflammatory diseases such as arthritis.
Ehling
Angela
A
Department of Internal Medicine I, University Hospital Regensburg, Germany.
Schäffler
Andreas
A
Herfarth
Hans
H
Tarner
Ingo H
IH
Anders
Sven
S
Distler
Oliver
O
Paul
Gisela
G
Distler
Jörg
J
Gay
Steffen
S
Schölmerich
Jürgen
J
Neumann
Elena
E
Müller-Ladner
Ulf
U
D000068879:Adalimumab; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C475418:ADIPOR1 protein, human; D052242:Adiponectin; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D000068879:Adalimumab