Inhibition of osteoclast differentiation and matrix metalloproteinase production by CD4+CD25+ T cells in mice.

Abstract

To reveal the mechanism of inflammation-accompanied osteoporosis, mouse CD11b cells and CD4+CD25+ T cells were cocultured. Our results showed that CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly less osteoclasts than those cocultured with CD4+CD25- T cells. The levels of MMP-7 and 9 in coculture supernatant were decreased significantly when CD11b+ monocytes and CD4+CD25+ T cells were cocultured comparing to the CD4+CD25- T cell group. These results highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis. The purpose of this study was to reveal the mechanism of inflammation-accompanied osteoporosis by examining the effect of CD4+CD25+ T cells on osteoclast formation, as well as the production of matrix metalloproteinases (MMP)-2, 3, 7, and 9 from osteoclasts. Mouse CD11b cells and CD4+CD25+ T cells were isolated using the microbead-based kits. Activated CD11b cells and CD4+CD25+ T were cocultured. CD4+CD25- T cells were used as controls. Osteoclasts were evaluated by counting the average of tartrate-resistant acid phosphatase-positive multinucleated large cells among five high-power fields (×200). After 2 days of coculture, supernatants were harvested for MMP measurement (by ELISA). At day 7, the CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly (both p < 0.01) less osteoclasts (3.4 ± 0.8) than those cocultured with CD4+CD25- T cells (16.2 ± 1.3) and those cultured alone (16.2 ± 2.7). The supernatant levels of MMP-7 and 9 were decreased significantly (p < 0.01) when CD11b+ monocytes and CD4+CD25+ T cells were cocultured compared to the other two conditions. The decreased CD4+CD25+ T cells may cause an overproduction of MMP-7 and 9 from osteoclasts, which highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis.