切换至 "中华医学电子期刊资源库"

中华关节外科杂志(电子版) ›› 2018, Vol. 12 ›› Issue (03) : 401 -404. doi: 10.3877/cma.j.issn.1674-134X.2018.03.018

所属专题: 文献

综述

成骨与破骨细胞促红细胞生成素肝细胞受体B4/肝配蛋白B2双向信号通路
葛于伟1, 朱振安1, 毛远青1,()   
  1. 1. 200011 上海交通大学医学院附属第九人民医院,上海市骨科实验室
  • 收稿日期:2017-08-21 出版日期:2018-06-01
  • 通信作者: 毛远青
  • 基金资助:
    国家自然科学基金(NO:81572158)

Bi-directional signaling pathway of erythropoietin-producing hepatocyte receptors between osteoblasts and osteoclasts

Yuwei Ge1, Zhen’an Zhu1, Yuanqing Mao1,()   

  1. 1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
  • Received:2017-08-21 Published:2018-06-01
  • Corresponding author: Yuanqing Mao
  • About author:
    Corresponding author: Mao Yuanqing, Email:
引用本文:

葛于伟, 朱振安, 毛远青. 成骨与破骨细胞促红细胞生成素肝细胞受体B4/肝配蛋白B2双向信号通路[J]. 中华关节外科杂志(电子版), 2018, 12(03): 401-404.

Yuwei Ge, Zhen’an Zhu, Yuanqing Mao. Bi-directional signaling pathway of erythropoietin-producing hepatocyte receptors between osteoblasts and osteoclasts[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2018, 12(03): 401-404.

成骨细胞与破骨细胞以直接接触的方式共同调控骨重建平衡,这也决定了两者的不可分割性。最新研究表明前破骨细胞肝配蛋白(Ephrin)B2与成骨细胞膜上促红细胞生成素肝细胞受体(Eph)B4受体的直接接触来调控骨稳态平衡。具有EphrinB2配体的前破骨细胞可通过直接接触具有EphB4受体的前成骨细胞从而触发各自相应的下游信号转导分子。通过激活成骨细胞膜表面Eph受体而起正向作用,进一步去抑制下游信号转导分子RhoA活性促进前体细胞分化成熟。反之,EphrinB2配体的激活起到反向作用,抑制破骨相关转录因子的C-fos/NFATc1转录级联反应来抑制前破骨细胞的分化,磨损颗粒导致的骨溶解会使破骨细胞上EphrinB2配体表达明显升高,并且会促进NFATc1的高表达,可以通过这种双向信号的机制来减弱甚至是抑制磨损颗粒导致的破骨细胞的进一步分化。

The balance of bone remodeling is regulated by direct contact between osteoblasts and osteoclasts, which also determines the indivisibility of the two. Recent studies have shown that erythropoietin producing hepatomocellular receptor interacting protein (Ephrin) ligand B2 in pre-osteoclasts and erythropoietin-producing hepatocyte(Eph)receptor B4 on the membrane of osteoblasts regulate bone homeostasis through direct contact, thereby activating downstream signaling pathways. Forward signaling: the activation of downstream signaling molecules Ras homolog gene family member A (Rho A) activity by the activation of Eph receptors on the surface of osteoblast membranes promotes the differentiation and maturation of pre-osteoclasts. Reverse signaling: the activation of EphrinB2 ligands plays a reverse role in inhibiting the osteoclast differentiation by inhibiting the C-fos/NFATc1 transcriptional cascade of osteoclast-related transcription factors. Osteolysis caused by wear particles can significantly increase the expression of ephrinB2 ligand on osteoclasts, and wear particles can promote high expression of NFATc1. However, bidirectional signaling pathway can be used to reduce or even inhibit the further differentiation of osteoclasts caused by wear particles.

[1]
Wang L, Zhang J, Wang C, et al. Low concentrations of TNF‐α promote osteogenic differentiation via activation of the EphrinB2-EphB4 signalling pathway[J]. Cell Proliferation, 2017, 50(1):1-9.
[2]
Pennisi A, Ling W, Li X, et al. The EphrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth[J]. Blood, 2009, 114(9):1803-1812.
[3]
Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signalling[J]. Nat Rev Mol Cell Biol, 2002, 3(7):475-486.
[4]
Nakamoto M. Eph receptors and Ephrins[J]. Int J Biochem Cell Biol, 2000, 18(1):7-12.
[5]
Jensen PL. Eph receptors and Ephrins[J]. Stem Cells, 2000, 18(1):63-64.
[6]
Egea J, Klein R. Bidirectional Eph-ephrin signaling during axon guidance[J]. Trends Cell Biol, 2007, 17(5):230-238.
[7]
Zhao C, Irie N, Takada Y, et al. Bidirectional EphrinB2-EphB4 signaling controls bone homeostasis[J]. Cell Metab, 2006, 4(2):111-121.
[8]
Pasquale EB. Eph-Ephrin bidirectional signaling in physiology and disease[J]. Cell, 2008, 133(1):38-52.
[9]
Himanen JP, Chumley MJ, Lackmann M, et al. Repelling class discrimination: Ephrin-A5 binds to and activates EphB2 receptor signaling[J]. Nat Neurosci, 2004, 7(5):501-509.
[10]
Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases:VEGFs,angiopoietins,and Ephrins in vascular development[J]. Genes Dev, 1999, 13(9):1055-1066.
[11]
Harada&amp SI. Rodan G A.control of osteoblast function and regulation of bone mass[J]. Nature, 2003, 423(6937):349-355.
[12]
Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis,lymphocyte development and lymphnode organogenesis[J]. Nature, 1999, 397(6717):315-323.
[13]
Harmey D, Stenbeck G, Nobes CD, et al. Regulation of osteoblast differentiation by pasteurella multocida toxin(PMT):a role for Rho GTPase in bone formation[J]. J Bone Miner Res, 2004, 19(4):661-670.
[14]
Mcbeath R, Pirone DM, Nelson CM, et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment[J]. Dev Cell, 2004, 6(4):483-495.
[15]
Martin T J, Allan E H, Ho P W, et al. Communication between ephrinB2 and EphB4 within the osteoblast lineage.[J]. Adv Exp Med Biol, 2009, 658:51-60.
[16]
Allan EH, Hausler KD, Wei T, et al. EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts[J]. J Bone Miner Res, 2008, 23(8):1170-1181.
[17]
Irie F, Yamaguchi Y. EphB receptors regulate dendritic spine development via intersectin,Cdc42 and N-WASP[J]. Nat Neurosci, 2002, 5(11):1117-1118.
[18]
Penzes P, Beeser A, Chernoff J, et al. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin[J]. Neuron, 2003, 37(2):263-274.
[19]
Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development[J]. Dev Cell, 2002, 2(4):389-406.
[20]
Kodama H, Nose M, Niida S, et al. Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells[J]. J Exp Med, 1991, 173(5):1291-1294.
[21]
Matsuo K, Irie N. Osteoclast-osteoblast communication[J]. Arch Biochem Biophys, 2008, 473(2):201-209.
[22]
Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and Calcium metabolism[J]. Proc Natl Acad Sci U S A, 2000, 97(4):1566-1571.
[23]
毛英杰,黄旭,赵鹃,等. EphB4/EphrinB2逆向信号对RAW264.7破骨细胞分化中PDZ结构域蛋白表达变化的研究[J]. 生物化学与生物物理进展,2011, 38(5):464-472.
[24]
Makinen T, Adams RH, Bailey J, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature[J]. Genes Dev, 2005, 19(3):397-410.
[25]
Arvanitis D, Davy A. Eph/Ephrin signaling: networks[J]. Genes Dev, 2008, 22(4):416-429.
[26]
Pasquale EB. Eph receptor signalling casts a wide net on cell behaviour[J]. Nat Rev Mol Cell Biol, 2005, 6(6):462-475.
[27]
Poliakov A, Cotrina M, Wilkinson DG. Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly[J]. Dev Cell, 2004, 7(4):465-480.
[1] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[2] 凡军, 曹丽萍. 异鼠李素激活p38信号促进鼠间充质干细胞成骨分化[J]. 中华关节外科杂志(电子版), 2021, 15(04): 432-437.
[3] 陈玉书, 谢慧峰, 张燕红, 白波, 陈艺, 张姝江. 甲状旁腺激素在骨软骨组织中的应用进展[J]. 中华关节外科杂志(电子版), 2021, 15(02): 214-218.
[4] 凡军, 曹丽萍. 体外研究橙皮苷抑制钛颗粒介导的破骨细胞分化[J]. 中华关节外科杂志(电子版), 2020, 14(06): 698-702.
[5] 刘鹏, 邓亚鹏, 曹国定, 高余, 封国超, 刘军, 甄平. 人工关节置换术后假体无菌性松动的研究进展[J]. 中华关节外科杂志(电子版), 2020, 14(03): 346-351.
[6] 伏洪玲, 刘瀚旻. 支气管肺发育不良及肺动脉高压有关信号通路研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(05): 497-505.
[7] 蒋敏, 谢艳艳, 姚延娇, 卢丹. Notch信号通路与妊娠相关疾病发生与发展的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(05): 519-526.
[8] 林伟斌, 朱聪, 洪海森, 黄国锋, 高明明, 吴进, 沙漠, 林灿斌, 陈娜娜, 张晓旭, 丁真奇. 体外周期性压应力对兔胫骨骨折愈合过程成骨与破骨细胞增殖分化能力的影响[J]. 中华损伤与修复杂志(电子版), 2021, 16(04): 289-300.
[9] 陈伟洋, 田俊, 韦曦. 硅离子在骨组织修复再生领域的作用[J]. 中华口腔医学研究杂志(电子版), 2021, 15(06): 375-381.
[10] 郑慧敏, 夏贤友, 刘梦, 姚晓雨, 隋磊. 整联蛋白在骨重建中的作用[J]. 中华口腔医学研究杂志(电子版), 2021, 15(02): 124-128.
[11] 骆鋆攀, 卢嘉蕊, 权晶晶. 破骨细胞融合蛋白的研究进展[J]. 中华口腔医学研究杂志(电子版), 2020, 14(04): 207-213.
[12] 单臻, 李雯, 范远键, 林泽飞, 林颖, 王深明. miR-223通过IGF-1R及NFIA调控乳腺癌细胞及破骨细胞功能的研究[J]. 中华普通外科学文献(电子版), 2020, 14(06): 406-410.
[13] 郭嘉瑜, 邱涛, 喻博. 泛素-蛋白酶体系统在肝缺血再灌注损伤中的研究进展[J]. 中华移植杂志(电子版), 2022, 16(01): 49-54.
[14] 王继荣, 暴一众, 唐颖, 吕晓玲, 杨舟鑫. 吴茱萸碱抑制破骨细胞分化延缓骨丢失的研究[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(02): 86-92.
[15] 房修罗, 赵太云, 陆兴俊. 康复新液联合美沙拉嗪对溃疡性结肠炎活动期患者HMGB1、MCP-1、SOCS-3和Beclin1表达的影响[J]. 中华临床医师杂志(电子版), 2022, 16(03): 246-251.
阅读次数
全文


摘要