Interleukin - 10 이 interleukin - 1B 로 유도되는 골흡수에 미치는 효과

Abstract

The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, interleukin-lj3(IL-1p)-induced bone resorption is me- diated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor a(TNF a) released from osteoblasts. Since these cytoki- nes (GM CSF, IL 6, TNF a) are produced by not only osteoblasts but also monocytes, and interleukin 10(I1 10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM CSF, IL 6, and TNF a by osteoblasts, then control IL lp induced bone resorption. Therefore, the aims of the present study were to examine the effects of IL 10 on bone resorption. The sixten or seventeen day pregnant ICR mice were injected with "Ca and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with Ca were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopol- ysaccharide(LPS), TNF a, IL la, IL 8, IL lj3, and IL a, Then, IL 10 and interfe ron y (IFN y) were added to calvarial medium, in an attempt to evaluate the effect of IL lp induced bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL 6, TNF a, and GM CSF produced from mouse calvarial cells were investigated in response to IL 1p alone and simultaneously adding f IL 1p and IL 10. The degree of bone resorption was expressed as the ratio of "Ca release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml; the ratio of "Ca release, 1.14+- 0.07). Also IL lp(1 ng/ml), IL la(1 ng/ml), and TNF a(1 ng/ml) resulted in bone resorption(the rations of "Ca release, 1.61+ 0.26, 177+ 0.03, 1.20+ 0.15 respectively), but IL 8 did not(the ratio of Ca release, 0.93+- 0.12). The ratios of Ca release in response to IL 10(400 ng/ml) and IFN y(100 ng/ml) were 1.24+- 0.12 and 1.08+- 0.04 respectively, hence these cytokines inhibited IL 1p(1 ng/ml) induced bone resorption(the ratio of "Ca release 1.65+-0.24). While IL-lp(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures(20+-11), simultaneou-sly adding IL lj3(1 ng/ml) and IL 10(400 ng/ml) decreased the number of these cells(2+- 2). Nevertheless, IL 10(400 ng/ml) did not affect the IL 6, GM CSF, and TNF a secretion from IL 1p(1 ng/ml) activated mouse calvarial cells. From the above results, it may be suggested that IL 10 inhibites IL p induced osteoc- last differntiation and bone resorption. However, the inhibitory effect of IL 10 on the osteoclast formation seems to be mediated not by the reduction of IL 6, GM CSF, and TNF a production, but by other mechanisms.