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Connexins和Pannexins在骨细胞交流中的作用

刘文静 张德茂 周学东 谢静

刘文静, 张德茂, 周学东, 等. Connexins和Pannexins在骨细胞交流中的作用[J]. 四川大学学报(医学版), 2020, 51(6): 771-776. doi: 10.12182/20201160102
引用本文: 刘文静, 张德茂, 周学东, 等. Connexins和Pannexins在骨细胞交流中的作用[J]. 四川大学学报(医学版), 2020, 51(6): 771-776. doi: 10.12182/20201160102
LIU Wen-jing, ZHANG De-mao, ZHOU Xue-dong, et al. The Role of Connexins and Pannexins in the Cell Communications of Bone Cells[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2020, 51(6): 771-776. doi: 10.12182/20201160102
Citation: LIU Wen-jing, ZHANG De-mao, ZHOU Xue-dong, et al. The Role of Connexins and Pannexins in the Cell Communications of Bone Cells[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2020, 51(6): 771-776. doi: 10.12182/20201160102

栏目: 口腔医学进展

Connexins和Pannexins在骨细胞交流中的作用

doi: 10.12182/20201160102
基金项目: 国家自然科学基金(No.81600840、No.81771047)资助
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    E-mail:xiejing@scu.edu.cn

The Role of Connexins and Pannexins in the Cell Communications of Bone Cells

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  • 摘要: Connexins和Pannexins在骨细胞和成骨细分化、细胞内信号转导、维持骨平衡以及骨再生中起着重要作用。本文就Connexins介导的缝隙连接及Pannexins介导的半通道在骨中的研究进展和局限性进行综述。目前的研究已经阐明这些分子以缝隙连接的形式或是独立的半通道的形式传递外界刺激到骨骼系统。然而,对于Connexins和Pannexins家族成员在骨发育和骨稳态中其他类型细胞如成骨细胞前体、骨髓间充质干细胞等,在维持正常生物学行为中的作用所知甚少。此外,目前Connexins家族中研究最多的成员是Connexin43 (Cx43),其他成员在骨骼发育中的作用与机制尚缺乏研究。基因编辑动物模型为研究Connexins和Pannexins在骨骼系统中的作用提供了基本的信息,但是 Connexins和Pannexins之间的异同仍然有待发现。将一种特定功能定位于Connexins或Pannexins对骨作用刺激和骨骼疾病的影响仍然是一个难题,其困扰是通道之间药理选择性重叠、其他亚型的补偿、评估通道功能的方法差异,以及与转基因小鼠模型相关的基因改变。因此,需要更好的工具和研究途径来了解这些通道在骨和软骨中的作用。未来研究的一个基本任务是找到特定的可以调节Connexins或Pannexins亚型的化合物,使其能够作为药物制剂治疗骨骼疾病,为改善骨骼健康、治疗骨骼系统的疾病开发新的治疗策略提供可能。
  • [1] PLOTKIN L I, STAINS J P. Connexins and pannexins in the skeleton: gap junctions, hemichannels and more. Cell Mol Life Sci,2015,72(15): 2853–2867. doi: 10.1007/s00018-015-1963-6
    [2] DONAHUE H J, QU R W, GENETOS D C. Joint diseases: from connexins to gap junctions. Nat Rev Rheumatol,2018,14(1): 42–51. doi: 10.1038/nrrheum.2017.204
    [3] PLOTKIN L I, DAVIS H M, CISTERNA B A, et al. Connexins and pannexins in bone and skeletal muscle. Curr Osteoporos Rep,2017,15(4): 326–334. doi: 10.1007/s11914-017-0374-z
    [4] BRÜCHER B L, JAMALL I S. Cell-cell communication in the tumor microenvironment, carcinogenesis, and anticancer treatment. Cell Physiol Biochem,2014,34(2): 213–243. doi: 10.1159/000362978
    [5] KUMAR V, COUSER N L, PANDYA A. Oculodentodigital dysplasia: a case report and major review of the eye and ocular adnexa features of 295 reported cases. Case Rep Ophthalmol Med, 2020, 4: 6535974[2020-05-25]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165356/. doi: 10.1155/2020/6535974.
    [6] 黄卫民, 张小敏, 陶亮. 细胞缝隙连接与骨及相关疾病研究进展. 新疆医科大学学报,2016,39(11): 1474–1477. doi: 10.3969/j.issn.1009-5551.2016.11.032
    [7] ROY S, JIANG J X, LI A F, et al. Connexin channel and its role in diabetic retinopathy. Prog Retin Eye Res,2017,61: 35–59. doi: 10.1016/j.preteyeres.2017.06.001
    [8] BEYER E C, BERTHOUD V M. Gap junction gene and protein families: connexins, innexins, and pannexins. Biochim Biophys Acta Biomembr,2018,1860(1): 5–8. doi: 10.1016/j.bbamem.2017.05.016
    [9] RODRÍGUEZ-SINOVAS A, RUIZ-MEANA M, DENUC A, et al. Mitochondrial Cx43, an important component of cardiac preconditioning. Biochim Biophys Acta Biomembr,2018,1860(1): 174–181. doi: 10.1016/j.bbamem.2017.06.011
    [10] TOTLAND M Z, RASMUSSEN N L, KNUDSEN L M, et al. Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications. Cell Mol Life Sci,2020,77(4): 573–591. doi: 10.1007/s00018-019-03285-0
    [11] EPIFANTSEVA I, SHAW R M. Intracellular trafficking pathways of Cx43 gap junction channels. Biochim Biophys Acta Biomembr,2018,1860(1): 40–47. doi: 10.1016/j.bbamem.2017.05.018
    [12] HERVE J C, DERANGEON M. Gap-junction-mediated cell-to-cell communication. Cell Tissue Res,2013,352(1): 21–31. doi: 10.1007/s00441-012-1485-6
    [13] WILLEBRORDS J, MAES M, CRESPO YANGUAS S, et al. Inhibitors of Connexin and Pannexin channels as potential therapeutics. Pharmacol Ther,2017,180: 144–160. doi: 10.1016/j.pharmthera.2017.07.001
    [14] SCEMES E, VELÍŠKOVÁ J. Exciting and not so exciting roles of Pannexins. Neurosci Lett,2019,695: 25–31. doi: 10.1016/j.neulet.2017.03.010
    [15] CARPINTERO-FERNANDEZ P, GAGO-FUENTES R, WANG H Z, et al. Intercellular communication via gap junction channels between chondrocytes and bone cells. Biochim Biophysica Acta Biomembr,2018,1860(12): 2499–2505. doi: 10.1016/j.bbamem.2018.09.009
    [16] LIU W, ZHANG D, LI X, et al. TGF-β1 facilitates cell-cell communication in osteocytes via Connexin43- and Pannexin1-dependent gap junctions. Cell Death Discov, 2019, 5: 141[2020-05-25]. https://www.nature.com/articles/s41420-019-0221-3. doi: 10.1038/s41420-019-0221-3.
    [17] PLOTKIN L I, LAIRD D W, AMEDEE J. Role of Connexins and Pannexins during ontogeny, regeneration, and pathologies of bone. BMC Cell Biol, 2016, 17 (Suppl 1): 19[2020-05-25]. https://bmcmolcellbiol.biomedcentral.com/articles/ 10.1186/s12860-016-0088-6. doi: 10.1186/s12860-016-0088-6.
    [18] 陈骞, 蒋科, 陈路, 等. 连接蛋白43在骨关节炎发病机制中的研究进展. 川北医学院学报,2016,31(6): 799–804. doi: 10.3969/j.issn.1005-3697.2016.06.006
    [19] STAINS J P, CIVITELLI R. Connexins in the skeleton. Semin Cell Dev Biol,2016,50: 31–39. doi: 10.1016/j.semcdb.2015.12.017
    [20] PACHECO-COSTA R, DAVIS H M, SORENSON C, et al. Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain. Bone,2015,81: 632–643. doi: 10.1016/j.bone.2015.09.011
    [21] LIN F X, ZHENG G Z, CHANG B, et al. Connexin 43 modulates osteogenic differentiation of bone marrow stromal cells through gsk-3beta/beta-catenin signaling pathways. Cell Physiol Biochem,2018,47(1): 161–175. doi: 10.1159/000489763
    [22] BUO A M, TOMLINSON R E, EIDELMAN E R, et al. Connexin43 and Runx2 interact to affect cortical bone geometry, skeletal development, and osteoblast and osteoclast function. J Bone Miner Res,2017,32(8): 1727–1738. doi: 10.1002/jbmr.3152
    [23] WU X T, SUN L W, YANG X, et al. The potential role of spectrin network in the mechanotransduction of MLO-Y4 osteocytes. Sci Rep, 2017, 7: 40940[2020-05-25]. https://www.nature.com/articles/srep40940. doi: 10.1038/srep40940.
    [24] PLOTKIN L I, SPEACHT T L, DONAHUE H J. Cx43 and mechanotransduction in bone. Curr Osteoporos Rep,2015,13(2): 67–72. doi: 10.1007/s11914-015-0255-2
    [25] BATRA N, RIQUELME M A, BURRA S, et al. Direct regulation of osteocytic Connexin 43 hemichannels through AKT kinase activated by mechanical stimulation. J Biol Chem,2014,289(15): 10582–10591. doi: 10.1074/jbc.M114.550608
    [26] RIQUELME M A, BURRA S, KAR R, et al. Mitogen-activated protein kinase (MAPK) activated by prostaglandin E2 phosphorylates Connexin 43 and closes osteocytic hemichannels in response to continuous flow shear stress. J Biol Chem,2015,290(47): 28321–28328. doi: 10.1074/jbc.M115.683417
    [27] BUO A M, STAINS J P. Gap junctional regulation of signal transduction in bone cells. FEBS Lett,2014,588(8): 1315–1321. doi: 10.1016/j.febslet.2014.01.025
    [28] RIQUELME M A, CARDENAS E R, XU H, et al. The role of Connexin channels in the response of mechanical loading and unloading of bone. Int J Mol Sci, 2020, 21(3): 1146[2020-05-25]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038207/. doi: 10.3390/ijms21031146.
    [29] WEI C J, FRANCIS R, XU X, et al. Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells. J Biol Chem,2005,280(20): 19925–19936. doi: 10.1074/jbc.M412921200
    [30] CHUNG D J, CASTRO H M, WATKINS M. Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of Connexin43. J Cell Sci,2006,119(Pt 20): 4187–4198.
    [31] PACHECO-COSTA R, HASSAN I, REGINATO R D, et al. High bone mass in mice lacking Cx37 because of defective osteoclast differentiation. J Biol Chem,2014,289(12): 8508–8520. doi: 10.1074/jbc.M113.529735
    [32] BIVI N, CONDON K W, ALLEN M R, et al. Cell autonomous requirement of Connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res,2012,27(2): 374–389. doi: 10.1002/jbmr.548
    [33] CHAIBLE L M, SANCHES D S, COGLIATI B, et al. Delayed osteoblastic differentiation and bone development in Cx43 knockout mice. Toxicol Pathol,2011,39(7): 1046–1055. doi: 10.1177/0192623311422075
    [34] WATKINS M, GRIMSTON S K, NORRIS J Y, et al. Osteoblast Connexin43 modulates skeletal architecture by regulating both arms of bone remodeling. Mol Biol Cell,2011,22(8): 1240–1251. doi: 10.1091/mbc.e10-07-0571
    [35] HASHIDA Y, NAKAHAMA K, SHIMIZU K, et al. Communication-dependent mineralization of osteoblasts via gap junctions. Bone, 2014, 61: 19-26[2020-05-25]. https://doi.org/10.1016/j.bone.2013.12.031.
    [36] LLOYD S A, LOISELLE A E, ZHANG Y, et al. Evidence for the role of connexin 43-mediated intercellular communication in the process of intracortical bone resorption via osteocytic osteolysis. BMC Musculoskelet Disord, 2014, 15: 122[2020-05-25]. https://bmcmusculoskeletdisord.biomedcentral.com/articles/ 10.1186/1471-2474-15-122. doi: 10.1186/1471-2474-15-122.
    [37] SADR-ESHKEVARI P, ASHNAGAR S, RASHAD A, et al. Bisphosphonates and Connexin 43: a critical review of evidence. Cell Commun Adhes,2014,21(5): 241–247. doi: 10.3109/15419061.2014.927869
    [38] SMIT M A, VAN KINSCHOT C M J, VAN DER LINDEN J, et al. Clinical guidelines and PTH measurement: does assay generation matter? Endocr Rev,2019,40(6): 1468–1480. doi: 10.1210/er.2018-00220
    [39] CHUNG D J, CASTRO C H M, WATKINS M, et al. Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of Connexin43. J Cell Sci,2006,119(20): 4187–4198. doi: 10.1242/jcs.03162
    [40] RIQUELME M A, CARDENAS E R, XU H, et al. The role of Connexin channels in the response of mechanical loading and unloading of bone. Int J Mol Sci, 2020, 21(3): 1146[2020-05-25]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038207/. doi: 10.3390/ijms21031146.
    [41] GRIMSTON S K, BRODT M D, SILVA M J, et al. Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the Connexin43 gene (Gja1). J Bone Miner Res,2008,23(6): 879–886. doi: 10.1359/jbmr.080222
    [42] LOISELLE A E, PAUL E M, LEWIS G S, et al. Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing. J Orthop Res,2013,31(1): 147–154. doi: 10.1002/jor.22178
    [43] MA L, HUA R, TIAN Y, et al. Connexin 43 hemichannels protect bone loss during estrogen deficiency. Bone Res, 2019, 7: 11[2020-05-25]. https://www.nature.com/articles/s41413-019-0050-2. doi: 10.1038/s41413-019-0050-2.
    [44] XU H Y, GU S M, RIQUELME M A, et al. Connexin 43 channels are essential for normal bone structure and osteocyte viability. J Bone Miner Res,2015,30(3): 436–448. doi: 10.1002/jbmr.2374
    [45] CHEN Y, CHEN M, XUE T, et al. Osteocytic Connexin 43 channels affect fracture healing. J Cell Physiol,2019,234(11): 19824–19832. doi: 10.1002/jcp.28581
    [46] BOND S R, LAU A, PENUELA S, et al. Pannexin 3 is a novel target for Runx2, expressed by osteoblasts and mature growth plate chondrocytes. J Bone Miner Res,2011,26(12): 2911–2922. doi: 10.1002/jbmr.509
    [47] ISHIKAWA M, IWAMOTO T, NAKAMURA T, et al. Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol,2011,193(7): 1257–1274. doi: 10.1083/jcb.201101050
    [48] ISHIKAWA M, IWAMOTO T, FUKUMOTO S, et al. Pannexin 3 inhibits proliferation of osteoprogenitor cells by regulating Wnt and p21 signaling. J Biol Chem,2014,289(5): 2839–2851. doi: 10.1074/jbc.M113.523241
    [49] HANSTEIN R, NEGORO H, PATEL N K, et al. Promises and pitfalls of a Pannexin1 transgenic mouse line. Front Pharmacol, 2013, 4: 61[2020-05-25]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648696/. doi: 10.3389/fphar.2013.00061.
    [50] ISHIKAWA M, YAMADA Y. The role of Pannexin 3 in bone biology. J Dent Res,2017,96(4): 372–379. doi: 10.1177/0022034516678203
    [51] IWAMOTO T, NAKAMURA T, DOYLE A, et al. Pannexin 3 regulates intracellular ATP/cAMP levels and promotes chondrocyte differentiation. J Biol Chem,2010,285(24): 18948–18958. doi: 10.1074/jbc.M110.127027
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出版历程
  • 收稿日期:  2020-06-23
  • 修回日期:  2020-10-30
  • 刊出日期:  2020-11-20

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