PDF(Pubmed)
Abstract：
IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.
摘要：
IL-34可促进破骨细胞分化和活化,这可能有助于激素诱导的股骨头坏死（ONFH）。在BALB/c和IL-34缺陷小鼠中构建动物模型以检测炎症细胞因子的相对表达。Micro-CT用于揭示内部结构。通过用IL-34条件培养基或M-CSF培养骨髓来源的巨噬细胞来诱导体外分化的破骨细胞。促炎细胞因子的相对表达，破骨细胞标记基因，实时定量RT-PCR检测相关通路分子,ELISA,和Westernblot。在ONFH患者血清和ONFH小鼠股骨头中均可检测到IL-34表达上调。IL-34缺陷小鼠表现出对ONFH诱导的抗性，小梁数量上调，小梁厚度,骨值分数，并下调小梁分离。另一方面,炎性细胞因子，如TNF-α，IFN-γ，IL-6、IL-12、IL-2和IL-17A，在IL-34缺陷型ONFH诱导的小鼠中显示表达减少。IL-34单独或与M-CSF协同作用以促进破骨细胞生成并激活ERK，STAT3和非典型NF-κB通路。这些数据表明，IL-34可以通过ERK促进破骨细胞的分化，STAT3和非典型NF-κB途径加重类固醇诱导的ONFH，和IL-34可以被视为治疗靶标。
