CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: different response of osteoblasts in the two groups.
Subchondral bone remodeling in osteoarthritis (OA) and rheumatoid arthritis (RA) is mainly characterized by the formation of osteophytes/fibrosis and by the presence of infiltrating cells associated to bone resorption. In this study we analyzed CC (cysteine cysteine motif) chemokine ligand (CCL)20 and CC chemokine receptor (CCR)6 function in subchondral bone tissue and osteoblasts isolated from OA and RA patients. CCL20/CCR6 expression was evaluated by immunohistochemical techniques in bone tissue from OA and RA patients. CCL20-functional tests were performed on osteoblasts isolated from OA and RA patients to evaluate enzymatic response and cell proliferation. Moreover, we assessed Akt phosphorylation as the major signaling pathway for CCL20. In bone tissue biopsies we found that osteoblasts from both OA and RA patients expressed CCR6 while CCL20 was expressed only by RA osteoblasts. Both CCR6 and CCL20 were highly expressed in osteocytes and mononuclear cells from only RA patients. CCL20-stimulated OA osteoblasts showed a significant increase in beta-N-acetylhexosaminidase release compared to RA. Conversely, a significant increase in cellular proliferation was found only in CCL20-stimulated RA osteoblasts associated to Akt phosphorylation. These data were confirmed in bone tissue biopsies. This study demonstrates a different expression of CCL20-positive osteoblasts in OA versus RA disease that seem to be associated with the presence of infiltrating mononuclear cells. Moreover, CCL20 stimulation resulted in a greater proliferative response in RA osteoblasts compared to OA osteoblasts, mediated by Akt signaling, while OA osteoblasts showed increased enzymatic activity, thus suggesting a differential role of this chemokine in OA and RA.
Lisignoli
Gina
G
Laboratorio di Immunologia e Genetica, Istituto Ortopedico Rizzoli, Bologna, Italy. gina.lisignoli@ior.it
Manferdini
Cristina
C
Codeluppi
Katia
K
Piacentini
Anna
A
Grassi
Francesco
F
Cattini
Luca
L
Filardo
Giuseppe
G
Facchini
Andrea
A
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D054418:Chemokine CCL20 / Q000378:metabolism* / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6; D051057:Proto-Oncogene Proteins c-akt; D001619:beta-N-Acetylhexosaminidases