| First Author | Takano S | Year | 2016 |
| Journal | Clin Exp Immunol | Volume | 183 |
| Issue | 1 | Pages | 143-9 |
| PubMed ID | 26400621 | Mgi Jnum | J:272215 |
| Mgi Id | MGI:6200865 | Doi | 10.1111/cei.12712 |
| Citation | Takano S, et al. (2016) Synovial macrophage-derived IL-1beta regulates the calcitonin receptor in osteoarthritic mice. Clin Exp Immunol 183(1):143-9 |
| abstractText | Recent studies have reported that calcitonin gene-related peptide (CGRP) contributes to joint pain. However, regulation of the CGRP/CGRP receptor signalling in osteoarthritis (OA) is not fully understood. To investigate the regulation of CGRP/CGRP receptor signalling by macrophages in the synovial tissue (ST) of OA joints, we characterized the gene expression profiles of CGRP and CGRP receptors in the ST of OA mice (STR/Ort). In addition, we examined whether macrophage depletion by the systemic injection of clodronate-laden liposomes affected the expression of CGRP and CGRP receptors in ST. CD11c(+) macrophages in the ST of STR/Ort and C57BL/6J mice were analysed by flow cytometry. Real-time polymerase chain reaction (PCR) was used to evaluate the expression of interleukin (IL)-1beta, CGRP, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in F4/80(+) and F4/80(-) cells. The effects of IL-1beta on the expression of CGRP and CLR by cultured synovial cells were also examined. The percentage of CD11c(+) macrophages in the ST of STR/Ort was higher than that in C57/BL6J mice. Notably, the F4/80(+) cell fraction expressed IL-1beta highly, whereas the F4/80(-) cell fraction expressed CGRP, CLR, and RAMP1 highly. In addition, expression of the IL-1beta and CLR genes was increased in ST, but was decreased upon macrophage depletion, and the IL-1beta treatment of cultured synovial cells up-regulated CLR. Taken together, the present findings suggest that synovial macrophages are the major producers of IL-1beta and regulators of CLR in OA mice. Therefore, macrophages and IL-1beta may be suitable therapeutic targets for treating OA pain. |
