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首页> 外文期刊>Cellular Physiology and Biochemistry >IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In Vitro
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IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In Vitro

机译：IL-6通过促进JAK2和RANKL的体外活性来增强成骨细胞介导的破骨细胞生成

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>Background/Aims: Evidence suggests that IL-6 affects bone mass by modulating osteocyte communication towards osteoclasts. However, the mechanism by which IL-6 enhances osteocyte-mediated osteoclastogenesis is unclear. We aimed to investigate the inflammatory factors in serum after orthodontic surgery and their relationship between osteocytes and osteoclasts. Methods: Serum was obtained from 10 orthognathic surgery patients, and inflammatory factors were detected by ELISA. We treated the osteocyte-like cell line MLO-Y4 with recombinant mouse IL-6 and IL-6 receptor (IL-6R), and used quantitative RT-PCR and Western blotting to explore Receptor activator of nuclear factor-?oB ligand (RANKL) expression at both the mRNA and protein level. MLO-Y4 cells were co-cultured with osteoclast precursor cells, and the formation of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. To explore the role of JAK2 in the osteocyte-mediated osteoclastogenesis, AG490, a JAK2 inhibitor, was used to inhibit the JAK2-STAT3 pathway in osteocytes. Results: In our study, we found that IL-6 and RANKL were stimulated in serum 3-7 days after orthognathic surgery. Therefore, IL-6 and IL-6 receptor enhanced the expression of RANKL at both the mRNA and protein level in MLO-Y4. Furthermore, when MLO-Y4 cells were co-cultured with osteoclast precursor cells, it significantly stimulated osteoclastogenesis. Our study indicated that osteocytes could promote osteoclastic differentiation and the formation of TRAP-positive multinucleated cells after stimulation with IL-6 and IL-6R. Our results also indicated that treatment with IL-6 and IL-6R increased RANKL mRNA expression and the RANKL/OPG expression ratio. Meanwhile, the phosphorylation of Janus kinase 2 (JAK2) and Signal transducer and activator of transcription (STAT3) also correlated with RANKL levels. Furthermore, we investigated the effects of a specific JAK2 inhibitor, AG490, on the expression of RANKL in osteocyte-like MLO-Y4 cells and osteocyte-mediated osteoclastogenesis. The results showed that AG490 inhibited (p)-JAK2 and RANKL expression. Osteoclastic differentiation was decreased after pretreatment in MLO-Y4 with mouse IL-6/IL-6R and AG490; therefore, we concluded that IL-6 increased osteocyte-mediated osteoclastic differentiation by activating JAK2 and RANKL. Conclusion: The effects of IL-6/il-6R and AG490 on osteocyte-mediated osteoclastogenesis contribute to our understanding of the role of inflammatory factors in the interaction between osteocytes and osteoclast precursors. IL-6 and RANKL are key factors for bone remodelling after the orthodontic surgery, and their roles in bone remodelling may be fundamental mechanisms accelerating tooth movement by orthodontic surgery.
机译：> 背景/目标： 有证据表明IL-6通过调节破骨细胞与破骨细胞的通讯来影响骨量。但是，IL-6增强骨细胞介导的破骨细胞形成的机制尚不清楚。我们的目的是调查正畸手术后血清中的炎性因子及其与破骨细胞和破骨细胞之间的关系。 方法： 从10例正颌外科手术患者中获取血清，并通过ELISA检测炎症因子。我们用重组小鼠IL-6和IL-6受体（IL-6R）处理了骨细胞样细胞系MLO-Y4，并使用定量RT-PCR和Western blotting来研究核因子-oB配体的受体激活剂（RANKL ）在mRNA和蛋白质水平上的表达。 MLO-Y4细胞与破骨细胞前体细胞共培养，并通过抗酒石酸酸性磷酸酶（TRAP）染色检测破骨细胞的形成。为了探讨JAK2在骨细胞介导的破骨细胞形成中的作用，使用了JAK2抑制剂AG490来抑制骨细胞中的JAK2-STAT3途径。 结果： 在我们的研究中，我们发现在正颌手术后3-7天血清中IL-6和RANKL受到刺激。因此，IL-6和IL-6受体在MLO-Y4的mRNA和蛋白水平上均增强了RANKL的表达。此外，当MLO-Y4细胞与破骨细胞前体细胞共培养时，它会显着刺激破骨细胞的生成。我们的研究表明，在用IL-6和IL-6R刺激后，骨细胞可以促进破骨细胞分化和TRAP阳性多核细胞的形成。我们的结果还表明，用IL-6和IL-6R处理可提高RANKL mRNA表达和RANKL / OPG表达比。同时，Janus激酶2（JAK2）和信号转导和转录激活因子（STAT3）的磷酸化也与RANKL水平相关。此外，我们研究了一种特定的JAK2抑制剂AG490对骨细胞样MLO-Y4细胞中RANKL表达和骨细胞介导的破骨细胞形成的影响。结果表明，AG490抑制（p）-JAK2和RANKL表达。用小鼠IL-6 / IL-6R和AG490在MLO-Y4中预处理后，破骨细胞的分化减少;因此，我们得出结论，IL-6通过激活JAK2和RANKL增强了骨细胞介导的破骨细胞分化。 结论： IL-6 / il-6R和AG490对骨细胞介导的破骨细胞形成的影响有助于我们理解炎症因子在破骨细胞与破骨细胞相互作用中的作用前体。 IL-6和RANKL是正畸手术后骨骼重塑的关键因素，它们在骨骼重塑中的作用可能是通过正畸手术加速牙齿运动的基本机制。

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