IL-1β promotes osteoclastogenesis by increasing the expression of IGF2 and chemokines in non-osteoclastic cells
IL-1β promotes osteoclastogenesis by increasing the expression of IGF2 and chemokines in non-osteoclastic cells
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IL-1β通过增加非破骨细胞中IGF2和趋化因子的表达来促进破骨细胞生成
DOI：
10.1016/j.jphs.2022.10.007
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发表时间：
2023
影响因子：
3.5
通讯作者：
Aoyama Mineyoshi
中科院分区：
文献类型：
--
作者：
Otsuka Yuto;Kondo Takao;Aoki Hiromasa;Goto Yoh;Kawaguchi Yohei;Waguri-Nagaya Yuko;Miyazawa Ken;Goto Shigemi;Aoyama Mineyoshi
由成骨细胞(OBS)和骨吸收破骨细胞(OCS)介导的骨重建维持着骨的结构和功能。OC的过度激活会导致骨质疏松和类风湿关节炎(RA)骨侵蚀等骨质破坏疾病。骨髓细胞(BMC)向OCs分化受骨微环境的调控。据报道，促炎细胞因子白介素1(IL-1)β促进破骨细胞的形成，并在类风湿关节炎相关的骨丢失中发挥重要作用。本研究探讨IL-1β通过微环境细胞对OC形成的影响。IL-1β在NF-κB受体激活剂和巨噬细胞集落刺激因子存在下处理小鼠骨髓细胞，可增加OCs的数量。实时荧光定量RT-PCR法检测到非OCS患者IL-1β、IL-1RI和IL-1RII基因表达水平均高于OCS患者。从小鼠骨髓细胞中去除不能分化为OCS的CD45OCs，可降低IL-1β介导的促进破骨细胞生成的作用。IL-1β可上调非OCS中诱导型一氧化氮合酶、胰岛素样生长因子2、趋化因子基质细胞衍生因子1、C-X3-C基序配体1和CXCL7的表达。在IL-1β存在的情况下，针对这些趋化因子和IGF2的中和抗体可抑制破骨细胞的生成。这些结果表明，IL-1β通过上调IGF2和趋化因子在非OCS中的表达来促进破骨细胞的形成。
Bone remodeling mediated by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCs) maintains bone structure and function. Excessive OC activation leads to bone-destroying diseases such as osteoporosis and bone erosion of rheumatoid arthritis (RA). Differentiation of OCs from bone marrow cells (BMCs) is regulated by the bone microenvironment. The proinflammatory cytokine interleukin (IL)-1β reportedly enhances osteoclastogenesis and plays important roles in RA-associated bone loss. The present study investigated the effect of IL-1β on OC formation via microenvironmental cells. Treating mouse BMCs with IL-1β in the presence of receptor activator of NF-κB ligand and macrophage colony-stimulating factor increased the number of OCs. Real-time RT-PCR revealed increased expression of the IL-1β, IL-1RI, and IL-1RII genes in non-OCs compared with OCs. Removing CD45−cells which cannot differentiate into OCs, from mouse BMCs reduced the IL-1β–mediated enhancement of osteoclastogenesis. IL-1β treatment upregulated the expression of inducible nitric oxide synthase, insulin-like growth factor 2 (IGF2), and the chemokines stromal cell derived factor 1, C-X3-C motif ligand 1 (CX3CL1), and CXCL7 in non-OCs. Neutralizing antibodies against these chemokines and IGF2 suppressed osteoclastogenesis in the presence of IL-1β. These results suggest that IL-1β enhances osteoclastogenesis by upregulating IGF2 and chemokine expression in non-OCs.