Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13.
BACKGROUND
Fibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis. These matrix fragments can stimulate production of multiple mediators of matrix destruction, including various cytokines and metalloproteinases. The purpose of this study was to discover novel mediators of cartilage destruction using fibronectin fragments as a stimulus.


METHODS
Human articular cartilage was obtained from tissue donors and from osteoarthritic cartilage removed at the time of knee replacement surgery. Enzymatically isolated chondrocytes in serum-free cultures were stimulated overnight with the 110 kDa alpha5beta1 integrin-binding fibronectin fragment or with IL-1, IL-6, or IL-7. Cytokines and matrix metalloproteinases released into the media were detected using antibody arrays and quantified by ELISA. IL-7 receptor expression was evaluated by flow cytometry, immunocytochemical staining, and PCR.


RESULTS
IL-7 was found to be produced by chondrocytes treated with fibronectin fragments. Compared with cells isolated from normal young adult human articular cartilage, increased IL-7 production was noted in cells isolated from older adult tissue donors and from osteoarthritic cartilage. Chondrocyte IL-7 production was also stimulated by combined treatment with the catabolic cytokines IL-1 and IL-6. Chondrocytes were found to express IL-7 receptors and to respond to IL-7 stimulation with increased production of matrix metalloproteinase-13 and with proteoglycan release from cartilage explants.


CONCLUSIONS
These novel findings indicate that IL-7 may contribute to cartilage destruction in joint diseases, including osteoarthritis.
Long
David
D
Section of Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina 27157, USA. dllong@wfubmc.edu
Blake
Simon
S
Song
Xiao-Yu
XY
Lark
Michael
M
Loeser
Richard F
RF
D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D004357:Drug Synergism; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D039081:Integrin alpha5beta1 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D007719:Knee Joint; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000494:pharmacology; D015854:Up-Regulation
D005353:Fibronectins; D039081:Integrin alpha5beta1; D007375:Interleukin-1; D015850:Interleukin-6; D015851:Interleukin-7; D007378:Interleukins; D010446:Peptide Fragments; D053509:Matrix Metalloproteinase 13