| First Author | Takano S | Year | 2017 |
| Journal | Clin Exp Immunol | Volume | 190 |
| Issue | 2 | Pages | 235-243 |
| PubMed ID | 28677145 | Mgi Jnum | J:266186 |
| Mgi Id | MGI:6200823 | Doi | 10.1111/cei.13007 |
| Citation | Takano S, et al. (2017) Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. Clin Exp Immunol 190(2):235-243 |
| abstractText | Nerve growth factor (NGF) functions to modulate osteoarthritis (OA)-associated pain. Although recent studies suggest that tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta mediate NGF activity in human synovial fibroblasts, the regulation of NGF expression in human synovial macrophages remains unclear. Here, we examined the role of macrophages in the production and regulation of synovial (SYN) NGF in osteoarthritic knee joints by examining the mRNA expression of TNF-alpha and IL-1beta in freshly isolated CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction) in synovial tissue from OA patients by quantitative polymerase chain reaction. We also examined the effects of IL-1beta and TNF-alpha on NGF mRNA expression in cultured CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction). In addition, to examine the contribution of macrophages to NGF, TNF-alpha and IL-1beta expression, we injected clodronate liposomes systemically into STR/Ort mice, an osteoarthritis animal model, to deplete macrophages. TNF-alpha and IL-1beta mRNA levels in CD14-positive cells from the SYN of OA patients was significantly higher than that in CD14-negative cells, while NGF expression did not differ markedly between the two cell fractions. In addition, treatment of human cultured CD14-positive and -negative cells with IL-1beta and TNF-alpha enhanced NGF mRNA and protein levels. Expression of NGF, IL-1beta and TNF-alpha was also reduced significantly in STR/Ort mice upon macrophage depletion. These findings suggest that IL-1beta and TNF-alpha regulate NGF expression and production in synovial macrophages and fibroblasts in osteoarthritic joints. |
