INTRODUCTION: Local inflammation plays a role in the pathophysiology of osteoarthritis (OA) and chemokines exert catabolic effects on articular cartilage either through paracrine and/or autocrine mechanisms. We sought to compare the expression levels of the chemokine (C-C motif) ligand 20 (CCL20) and its chemokine receptor 6 (CCR6) in donor and osteoarthritic (OA) cartilage and to investigate the role of CCL20 in the pathogenesis of OA and chondrocyte phenotype. METHODS: Cartilage/chondrocytes from donor and OA knee joints was analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. Effects of CCL20 on cytokines and mediators of cartilage degradation were examined by RT-PCR for mRNA expression levels, enzyme-linked immunosorbent assays, and proteoglycan (GAG) assays. RESULTS: CCL20 and CCR6 proteins were abundantly expressed in OA cartilage sections compared to donor sections as judged by immunohistochemistry. RT-PCR of cartilage extracts confirmed the predominance of CCL20/CCR6 mRNA expression in OA cartilage. CCL20 mRNA expression was low in donor chondrocytes but increased after stimulation with proinflammatory cytokines. mRNA expression levels of IL-6, cyclooxygenase-2, and iNOS were elevated in donor chondrocyte cultures treated with rhCCL20. The release of MMP1/13, PGE2, proteoglycan GAG fragments, and IL-6 from cartilage explant cultures was markedly augmented in the presence of CCL-20. CCL-20 stimulated MMP-13, ADAMTS-5, and col type X mRNA but inhibited col type II mRNA expression in freshly explanted and cultured cartilage specimens. CONCLUSIONS: CCL20/CCR6 may play an important role in the pathogenesis of OA by inducing changes in phenotype and catabolic gene expression in chondrocytes.
INTRODUCTION: Local inflammation plays a role in the pathophysiology of osteoarthritis (OA) and chemokines exert catabolic effects on articular cartilage either through paracrine and/or autocrine mechanisms. We sought to compare the expression levels of the chemokine (C-C motif) ligand 20 (CCL20) and its chemokine receptor 6 (CCR6) in donor and osteoarthritic (OA) cartilage and to investigate the role of CCL20 in the pathogenesis of OA and chondrocyte phenotype. METHODS: Cartilage/chondrocytes from donor and OA knee joints was analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. Effects of CCL20 on cytokines and mediators of cartilage degradation were examined by RT-PCR for mRNA expression levels, enzyme-linked immunosorbent assays, and proteoglycan (GAG) assays. RESULTS:CCL20 and CCR6 proteins were abundantly expressed in OA cartilage sections compared to donor sections as judged by immunohistochemistry. RT-PCR of cartilage extracts confirmed the predominance of CCL20/CCR6 mRNA expression in OA cartilage. CCL20 mRNA expression was low in donor chondrocytes but increased after stimulation with proinflammatory cytokines. mRNA expression levels of IL-6, cyclooxygenase-2, and iNOS were elevated in donor chondrocyte cultures treated with rhCCL20. The release of MMP1/13, PGE2, proteoglycan GAG fragments, and IL-6 from cartilage explant cultures was markedly augmented in the presence of CCL-20. CCL-20 stimulated MMP-13, ADAMTS-5, and col type X mRNA but inhibited col type II mRNA expression in freshly explanted and cultured cartilage specimens. CONCLUSIONS:CCL20/CCR6 may play an important role in the pathogenesis of OA by inducing changes in phenotype and catabolic gene expression in chondrocytes.
Authors: R Hromas; P W Gray; D Chantry; R Godiska; M Krathwohl; K Fife; G I Bell; J Takeda; S Aronica; M Gordon; S Cooper; H E Broxmeyer; M J Klemsz Journal: Blood Date: 1997-05-01 Impact factor: 22.113
Authors: Z Liu; Y Ren; A J Mirando; C Wang; M J Zuscik; R J O'Keefe; M J Hilton Journal: Osteoarthritis Cartilage Date: 2015-10-30 Impact factor: 6.576
Authors: Helene Kolstad Skovdahl; Jan Kristian Damås; Atle van Beelen Granlund; Ann Elisabet Østvik; Berit Doseth; Torunn Bruland; Tom Eirik Mollnes; Arne Kristian Sandvik Journal: Int J Mol Sci Date: 2018-10-20 Impact factor: 5.923