We examined the direct effects of Interleukin-7 (IL-7) on osteoclastogenesis in murine bone marrow cultures using cells from wild-type, IL-7 and IL-7 receptor deficient mice.

IL-7 inhibited OCL formation in M-CSF and RANKL (both at 30 ng/ml)-stimulated murine bone marrow cultures. Significant inhibitory effects were seen at 1 ng/ml (57%) and 10 ng/ml (86%). IL-7 also inhibited (P < 0.05) OCL formation in bone marrow cultures that were stimulated with vitamin D₃ (10^-8 M, 60%), bPTH (100 ng/ml, 54%) or RANKL alone (30 ng/ml, 50%). IL-7 (10 ng/ml) increased expression of the B-lymphocyte marker B220 from 40% to 86% of total non-adherent cells in cultures treated with M-CSF and RANKL. Bone marrow cells from IL-7 deficient (IL-7KO) mice showed a significant (P < 0.05) increase in TRAP(+) OCL numbers in cultures that were stimulated with vitamin D₃ (136 ± 13.3%), bPTH (196 ± 18.8%) or M-CSF and RANKL (160 ± 7.2%).

In contrast, in vitro osteoclast formation in bone marrow from IL-7 receptor deficient (IL-7R KO) mice showed a significant decrease in TRAP(+) OCL numbers in cultures that were stimulated with vitamin D₃, PTH, RANKL or M-CSF and RANKL. These results demonstrate that there are differences in the mechanisms regulating OCL formation between IL-7 KO and IL-7R KO cells.

It appears that IL-7 is a direct inhibitor of OCL formation in vitro based on results of adding IL-7 to WT cultures and the responses of IL-7 KO cells. It is unknown why IL-7R KO cells behave differently from IL-7 KO cells in vitro. However, it is possible that additional cytokines interact with IL-7R and loss of these signals contribute to the responses of IL-7R KO cells. Alternatively, IL-7 may interact with multiple receptors.