Oncostatin M 可增强 bFGF 刺激的成骨细胞样细胞中的骨保护素合成,但会减少巨噬细胞集落刺激因子的合成。

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Experimental and therapeutic medicine Pub Date : 2023-11-24 DOI:10.3892/etm.2023.12322
Tomoyuki Hioki, Junko Tachi, Kyohei Ueda, Rie Matsushima-Nishiwaki, Hiroki Iida, Osamu Kozawa, Haruhiko Tokuda
{"title":"Oncostatin M 可增强 bFGF 刺激的成骨细胞样细胞中的骨保护素合成,但会减少巨噬细胞集落刺激因子的合成。","authors":"Tomoyuki Hioki, Junko Tachi, Kyohei Ueda, Rie Matsushima-Nishiwaki, Hiroki Iida, Osamu Kozawa, Haruhiko Tokuda","doi":"10.3892/etm.2023.12322","DOIUrl":null,"url":null,"abstract":"Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c<i>-</i>Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"3 1","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells.\",\"authors\":\"Tomoyuki Hioki, Junko Tachi, Kyohei Ueda, Rie Matsushima-Nishiwaki, Hiroki Iida, Osamu Kozawa, Haruhiko Tokuda\",\"doi\":\"10.3892/etm.2023.12322\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c<i>-</i>Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.\",\"PeriodicalId\":12285,\"journal\":{\"name\":\"Experimental and therapeutic medicine\",\"volume\":\"3 1\",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-11-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental and therapeutic medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3892/etm.2023.12322\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and therapeutic medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3892/etm.2023.12322","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

骨重塑受到各种因素的严格控制,包括激素、自体类固醇和细胞因子。其中,OSM(oncostatin M)是一种由骨膜巨噬细胞产生的多功能细胞因子,是骨重塑的重要调节因子。巨噬细胞集落刺激因子(M-CSF)和骨蛋白激酶(osteoprotegerin)由成骨细胞分泌,在调节骨重塑过程中也起着举足轻重的作用。碱性成纤维细胞生长因子(bFGF)是骨重塑的一个关键调节因子,它与相应的受体[成纤维细胞生长因子受体(FGFR)]结合会引发 FGFR 的二聚化和活化,从而导致 FGFR 底物磷酸化,随后通过 Grb2 激活下游效应因子,包括丝裂原活化蛋白激酶(MAPK)。bFGF 可激活 MAPKs,导致成骨细胞样 MC3T3-E1 细胞合成骨保护素和血管内皮生长因子。在本研究中,OSM 对 bFGF 诱导的成骨细胞活化的影响主要体现在成骨细胞中骨蛋白gerin 和 M-CSF 的合成上。使用 ELISA 分析了骨保护gerin 和 M-CSF 的释放。使用逆转录定量 PCR 分析了骨保护gerin 和 M-CSF 的 mRNA 表达水平。p38 MAPK、应激活化蛋白激酶/c-Jun N-末端激酶(SAPK/JNK)和 p44/p42 MAPK 的磷酸化采用 Western 印迹法进行评估。OSM增强了bFGF诱导的骨保护gerin释放和bFGF刺激的骨保护gerin mRNA表达。相比之下,OSM 抑制了 bFGF 诱导的 M-CSF 释放和 bFGF 刺激的 M-CSF mRNA 表达。p38 MAPK抑制剂SB203580和SAPK/JNK抑制剂SP600125抑制了bFGF刺激的M-CSF释放,而p44/p42 MAPK上游激酶抑制剂PD98059未能抑制bFGF刺激的M-CSF释放。此外,OSM 还增强了 bFGF 诱导的 p38 MAPK 磷酸化,但减弱了 bFGF 刺激的 SAPK/JNK 磷酸化。相比之下,OSM 对 bFGF 诱导的 p44/p42 MAPK 磷酸化几乎没有影响。SB203580 显著降低了 OSM 对 bFGF 刺激的骨保护素释放的放大作用。这些结果有力地表明,OSM 可能对 bFGF 诱导的成骨细胞活化、p38 MAPK 上调和 SAPK/JNK 下调具有不同的作用,从而导致骨保护gerin 合成的增加和 M-CSF 合成的减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells.
Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Experimental and therapeutic medicine
Experimental and therapeutic medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
1.50
自引率
0.00%
发文量
570
审稿时长
1 months
期刊介绍:
期刊最新文献
Off‑label and unapproved pediatric drug utilization: A meta‑analysis. Multivariate analysis of blood parameters for predicting mortality in patients with hip fractures. New insights on the link between Epstein‑Barr virus infection and cognitive decline in neurodegenerative diseases (Review). Peptic ulcer induced by immune checkpoint inhibitors successfully treated with glucocorticoids: A report of three cases and a literature review. Different strategies for treating intracanal fractured instruments in a single tooth: A case report.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1