IL-37 inhibits osteoporosis via regulating M-CSF and inhibiting IL-6-JAK2/STAT3 signaling pathway / 中国免疫学杂志

ABSTRACT

Objective:To investigate the mechanism of IL-37 in inhibiting osteoporosis. Methods:Ninety-seven patients with osteoporosis and eighty-one fracture surgery patients without osteoporosis in our hospital from Jan 2013 to Dec 2015 were selected as study subjects. The serum level of IL-37 and IL-6 were detected. Construction of IL-37 transgenic mice, the C57BL/6J mice, IL-37 transgenic mice were set in sham operation group ( Sham ) , operation group ( ovariectomy, OVX ) respectively. The serum level of estrogen,alkaline phosphatase( ALP) ,calcium and phosphorus were detected after 8 weeks. The bilateral femur and spine of mice were collect after sacrifice,the morphology and structure of the femur were analyzed,and the bone density was measured by bone density me-ter. The bone marrow stromal cells( BMSCs) were isolated and cultured in vitro. The proliferation ability of BMSCs,expression of M-CSF and IL-6,and the activation of STAT3 were detected. IL-37 was transfected into mouse osteoblast MC3T3-E1 cell,M-CSF and IL-6 in cultured supernatant were measured by ELISA. Apoptosis of MC3T3-E1 cells were detected by flow cytometry. The activation of STAT3 was detected by Western blot. Results:The serum level of IL-37 in patients with osteoporosis were significantly lower than control group (P<0. 05),while IL-6 was significantly higher than control group(P<0. 05). The serum level of estrogen,calcium and phosphorus in OVX group of C57BL/6J mice and IL-37 transgenic mice were significantly lower than the sham operation group(P<0. 05),while the level of ALP was significantly higher than sham operation group ( P<0. 05 ) , but the serum level of calcium and phosphorus in OVX group of IL-37 transgenic mice were significantly higher than C57BL/6J mice(P<0. 05). The pathological section of femur and spine BMD showed that the bone tissue in C57BL/6J mice and IL-37 transgenic mice in OVX group were damaged and the bone density decreased significantly,but IL-37 transgenic mice was significantly better than C57BL/6J mice(P<0. 05). The proliferation ability BMSCs in OVX group of IL-37 transgenic mice was significantly higher than C57BL/6J,while the activation of STAT3 and expression of M-CSF were significantly lower than C57BL/6J(P<0. 05). The expression of M-CSF and IL-6 were inhibited after MC3T3-E1 cell was transfected with IL-37,and the activation of STAT3 were also inhibited after IL-37 transfection. The results of flow cytometry showed that IL-37 could significantly inhibit the apoptosis of MC3T3-E1 cells. Conclusion:The serum level of IL-37 in patients with osteoporosis decreased significantly. IL-37 may inhibit the proliferation of BMSCs and inhibit the apoptosis of osteoblasts by regulating the expression of M-CSF and the activation of IL-6-JAK2/STAT3 signaling pathway.