Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection
Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection
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DOI：
10.3390/ijms21082904
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Chen, Mei-Feng
中科院分区：
文献类型：
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作者：
Chang, Yuhan;Hsiao, Yi-min;Chen, Mei-Feng
由于脂多糖(LPS)介导的破骨细胞分化和骨丢失的作用，革兰氏阴性菌引起的假体周围关节感染(PJI)增加了再植后无菌性松动的风险。PJI患者滑液中IL-16的表达高于无关节感染的患者。因此，我们探讨了IL-16对骨骼的影响。我们在体外研究了IL-16对破骨细胞或成骨细胞分化的调节作用。采用脂多糖诱导的小鼠骨丢失模型，探讨抑制IL-16预防骨丢失的可能优势。IL-16直接激活p38和c-jun氨基末端激酶(JNK)/丝裂原活化蛋白激酶(MAPK)信号，并增加破骨细胞激活标志物，包括酒石酸抗性酸性磷酸酶(TRAP)、组织蛋白酶K和活化T细胞核因子1(NFATc1)。IL-16通过依赖JNK/MAPK信号通路激活NFATc1，直接诱导单核细胞分化为TRAP阳性破骨细胞样细胞。此外，IL-16不改变成骨细胞分化过程中碱性磷酸酶的活性或钙沉积。最后，在体内，抑制IL-16可以阻止脂多糖诱导的骨小梁丢失和破骨细胞的激活。IL-16通过JNK/NFATc1途径直接促进破骨细胞活化。抑制IL-16可能代表着治疗感染相关性骨丢失的新策略。
Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.