摘要
背景:成骨细胞,破骨细胞,骨细胞和软骨细胞之间的细胞间串扰与骨稳态的精确控制有关。这种细胞和分子信号的破坏将导致代谢性骨疾病,例如骨质疏松症。目前,许多抗骨质疏松症干预措施受到副作用,并发症和长期不耐受的限制。这篇综述旨在总结参与骨重建的骨细胞通讯及其在开发用于骨质疏松症的新药物中的用途。 方法:我们检索1980年1月1日至2018年1月1日的PubMed出版物,以鉴定相关和最新文献,总结骨质疏松症药物的评价和前景。详细的搜索词是“骨质疏松症”,“骨细胞”,“成骨细胞”,“破骨细胞”,“骨重塑”,“软骨细胞”,“骨质疏松症治疗”,“骨质疏松症治疗”,“双膦酸盐”,“ denosumab”,“选择性雌激素”受体调节剂(SERM)”,“ PTH”,“ romosozumab”,“ dkk-1拮抗剂”,“雷奈酸锶”。 结果:共纳入170篇论文。大约80篇论文描述了骨骼重建中涉及的骨细胞相互作用。其余的论文集中在骨质疏松症治疗的新领域和新领域。 结论:参与骨重塑的骨细胞间存在复杂的信号网络。细胞间通讯障碍可能是骨质疏松症的潜在机制。当前的抗骨质疏松疗法是有效的,但是同时具有某些缺点。恢复异常信号网络和个性化治疗对于理想的药物开发至关重要。
关键词: 成骨细胞,破骨细胞,骨细胞,骨稳态,骨质疏松症,治疗。
[http://dx.doi.org/10.1038/nature01658] [PMID: 12748652 ]
[http://dx.doi.org/10.1056/NEJMra053077] [PMID: 16723616 ]
[http://dx.doi.org/10.1016/j.bone.2009.03.671] [PMID: 19345750 ]
[http://dx.doi.org/10.1007/s12576-012-0212-0] [PMID: 22627708 ]
[http://dx.doi.org/10.1016/j.molmed.2004.12.004] [PMID: 15694870 ]
[http://dx.doi.org/10.1210/er.2006-0029] [PMID: 17200084 ]
[http://dx.doi.org/10.1093/ortho/25.2.101] [PMID: 9668992 ]
[http://dx.doi.org/10.2165/11587570-000000000-00000] [PMID: 21175240 ]
[http://dx.doi.org/10.1074/jbc.R109.041087] [PMID: 20501658 ]
[http://dx.doi.org/10.1002/jcb.10369] [PMID: 12532321 ]
[http://dx.doi.org/10.1073/pnas.87.18.7260] [PMID: 2169622 ]
[http://dx.doi.org/10.2174/187152812800392670] [PMID: 22280242 ]
[http://dx.doi.org/10.1038/s41467-017-02541-w] [PMID: 29352112 ]
[http://dx.doi.org/10.1016/S0092-8674(00)80209-3] [PMID: 9108485 ]
[http://dx.doi.org/10.1016/S0092-8674(00)81569-X] [PMID: 9568710 ]
[http://dx.doi.org/10.1359/jbmr.2000.15.11.2178] [PMID: 11092398 ]
[http://dx.doi.org/10.2174/1381612013397807] [PMID: 11375772 ]
[http://dx.doi.org/10.1007/s11154-014-9308-6] [PMID: 25557611 ]
[http://dx.doi.org/10.1038/nrd3705] [PMID: 22543469 ]
[http://dx.doi.org/10.1016/j.mce.2015.09.009] [PMID: 26365296 ]
[http://dx.doi.org/10.1038/nm.4076] [PMID: 27064449 ]
[http://dx.doi.org/10.1016/j.cell.2008.03.011] [PMID: 18394988 ]
[http://dx.doi.org/10.1101/gad.1973910] [PMID: 21078817 ]
[http://dx.doi.org/10.1016/j.tcb.2007.03.004] [PMID: 17420126 ]
[http://dx.doi.org/10.1242/jcs.00625] [PMID: 12808016 ]
[http://dx.doi.org/10.1359/jbmr.080324] [PMID: 18627264 ]
[http://dx.doi.org/10.1016/j.cmet.2006.05.012] [PMID: 16890539 ]
[PMID: 21373749 ]
[http://dx.doi.org/10.4161/cam.20888] [PMID: 22660185 ]
[http://dx.doi.org/10.1038/cdd.2015.14] [PMID: 25744024 ]
[http://dx.doi.org/10.1083/jcb.92.1.227] [PMID: 6976967 ]
[http://dx.doi.org/10.1074/jbc.M611781200] [PMID: 17690108 ]
[http://dx.doi.org/10.1038/s41413-017-0006-3] [PMID: 29507818 ]
[http://dx.doi.org/10.1073/pnas.1419714112] [PMID: 25733894 ]
[http://dx.doi.org/10.1083/jcb.201608002] [PMID: 28193701 ]
[http://dx.doi.org/10.2106/00004623-199173090-00022] [PMID: 1918129 ]
[http://dx.doi.org/10.1016/8756-3282(95)00186-H] [PMID: 8579905 ]
[http://dx.doi.org/10.1126/science.3201241] [PMID: 3201241 ]
[http://dx.doi.org/10.1038/nm.1979] [PMID: 19584867 ]
[http://dx.doi.org/10.1038/nm.2793] [PMID: 22729283 ]
[http://dx.doi.org/10.1038/77131] [PMID: 10888887 ]
[http://dx.doi.org/10.1016/S0092-8674(01)00206-9] [PMID: 11207362 ]
[http://dx.doi.org/10.1136/jmg.2005.036673] [PMID: 16118345 ]
[http://dx.doi.org/10.1016/S0002-9440(10)62269-9] [PMID: 15681830 ]
[http://dx.doi.org/10.1038/sj.emboj.7601430] [PMID: 17124500 ]
[http://dx.doi.org/10.1038/nature07713] [PMID: 19204730 ]
[http://dx.doi.org/10.1038/nm.2489] [PMID: 22019888 ]
[http://dx.doi.org/10.1172/JCI91086] [PMID: 29504949 ]
[http://dx.doi.org/10.1172/JCI69493] [PMID: 23908115 ]
[http://dx.doi.org/10.1002/jbmr.3436] [PMID: 29624737 ]
[http://dx.doi.org/10.1016/S1357-2725(03)00241-3] [PMID: 14592527 ]
[http://dx.doi.org/10.1016/j.jbiomech.2005.08.005] [PMID: 16176815 ]
[http://dx.doi.org/10.1210/er.2012-1026] [PMID: 23612223 ]
[http://dx.doi.org/10.1016/j.bbrc.2009.09.010] [PMID: 19737533 ]
[http://dx.doi.org/10.1016/j.bone.2016.06.016] [PMID: 27373501 ]
[http://dx.doi.org/10.1007/BF02409482] [PMID: 6797704 ]
[http://dx.doi.org/10.1016/8756-3282(92)90452-3] [PMID: 1419377 ]
[http://dx.doi.org/10.1016/j.bone.2007.12.224] [PMID: 18280232 ]
[http://dx.doi.org/10.1074/jbc.M413274200] [PMID: 15778503 ]
[http://dx.doi.org/10.1210/jc.2005-2370] [PMID: 16330810 ]
[http://dx.doi.org/10.1359/jbmr.090730] [PMID: 19594304 ]
[http://dx.doi.org/10.1002/jbmr.2514] [PMID: 25808845 ]
[http://dx.doi.org/10.1128/MCB.24.11.4677-4684.2004] [PMID: 15143163 ]
[http://dx.doi.org/10.1016/j.bone.2006.03.017] [PMID: 16730481 ]
[http://dx.doi.org/10.1136/ard.2010.132852] [PMID: 20858621 ]
[http://dx.doi.org/10.1074/jbc.M705092200] [PMID: 18089564 ]
[http://dx.doi.org/10.1210/me.2003-0498] [PMID: 14976225 ]
[http://dx.doi.org/10.1002/jcb.20599] [PMID: 16149051 ]
[http://dx.doi.org/10.1359/jbmr.1999.14.7.1123] [PMID: 10404012 ]
[http://dx.doi.org/10.1359/jbmr.2002.17.6.1015] [PMID: 12054156 ]
[http://dx.doi.org/10.1016/j.bbrc.2006.07.146] [PMID: 16904067 ]
[http://dx.doi.org/10.1016/j.tem.2009.12.004] [PMID: 20079660 ]
[http://dx.doi.org/10.1210/endo.133.4.7691577] [PMID: 7691577 ]
[http://dx.doi.org/10.1007/BF00298559] [PMID: 7895184 ]
[http://dx.doi.org/10.1056/NEJM198307143090206] [PMID: 6343879 ]
[http://dx.doi.org/10.1007/BF02554834] [PMID: 3924371 ]
[http://dx.doi.org/10.1038/nm.2452] [PMID: 21909105 ]
[http://dx.doi.org/10.1038/nm.2448] [PMID: 21909103 ]
[http://dx.doi.org/10.1371/journal.pone.0138189] [PMID: 26393791 ]
[http://dx.doi.org/10.1210/en.2014-1046] [PMID: 24877630 ]
[http://dx.doi.org/10.1002/jbmr.1941] [PMID: 23529793 ]
[http://dx.doi.org/10.1371/journal.pone.0025900] [PMID: 21991382 ]
[http://dx.doi.org/10.1074/jbc.M114.628313] [PMID: 25953900 ]
[http://dx.doi.org/10.1016/j.bone.2007.07.019] [PMID: 17855178 ]
[http://dx.doi.org/10.1002/jbmr.1567] [PMID: 22308018 ]
[http://dx.doi.org/10.1002/jcb.20449] [PMID: 15880692 ]
[http://dx.doi.org/10.1007/s00774-010-0199-7] [PMID: 20607327 ]
[http://dx.doi.org/10.1101/gad.965602] [PMID: 11937493 ]
[http://dx.doi.org/10.1242/dev.043281] [PMID: 19906842 ]
[http://dx.doi.org/10.1242/dev.069575] [PMID: 22190639 ]
[http://dx.doi.org/10.1016/j.joca.2005.07.012] [PMID: 16168681 ]
[http://dx.doi.org/10.1016/j.joca.2005.03.008] [PMID: 16243232 ]
[PMID: 11719548 ]
[http://dx.doi.org/10.1007/s10735-004-3839-1] [PMID: 15704000 ]
[http://dx.doi.org/10.1359/jbmr.071025] [PMID: 17967138 ]
[http://dx.doi.org/10.1172/JCI29463] [PMID: 17099775 ]
[http://dx.doi.org/10.1002/art.38195] [PMID: 24431282 ]
[http://dx.doi.org/10.1359/jbmr.061113] [PMID: 17144789 ]
[http://dx.doi.org/10.1007/s11657-013-0136-1] [PMID: 24113837 ]
[http://dx.doi.org/10.1007/s00198-012-2074-y] [PMID: 23079689 ]
[http://dx.doi.org/10.1002/jbmr.1745] [PMID: 22467094 ]
[http://dx.doi.org/10.1196/annals.1346.041] [PMID: 16831938 ]
[http://dx.doi.org/10.4065/83.9.1032] [PMID: 18775204 ]
[PMID: 11160603 ]
[http://dx.doi.org/10.1073/pnas.0601643103] [PMID: 16684881 ]
[http://dx.doi.org/10.1359/jbmr.1998.13.4.581] [PMID: 9556058 ]
[http://dx.doi.org/10.1056/NEJMoa030897] [PMID: 15028823 ]
[http://dx.doi.org/10.1001/jama.296.24.2927] [PMID: 17190893 ]
[http://dx.doi.org/10.1359/jbmr.080205] [PMID: 18558816 ]
[http://dx.doi.org/10.1210/jc.2009-1947] [PMID: 20173017 ]
[http://dx.doi.org/10.1359/jbmr.2000.15.4.613] [PMID: 10780852 ]
[http://dx.doi.org/10.1210/jc.2004-0952] [PMID: 15598694 ]
[http://dx.doi.org/10.1210/jc.2007-2803] [PMID: 18522980 ]
[http://dx.doi.org/10.1007/s00223-009-9263-5] [PMID: 19548019 ]
[http://dx.doi.org/10.1016/j.amjmed.2012.06.023] [PMID: 23177553 ]
[http://dx.doi.org/10.1359/JBMR.040305] [PMID: 15176987 ]
[http://dx.doi.org/10.1359/jbmr.081112] [PMID: 19016581 ]
[http://dx.doi.org/10.1359/jbmr.0809010] [PMID: 18767928 ]
[http://dx.doi.org/10.1016/S2213-8587(17)30138-9] [PMID: 28546097 ]
[http://dx.doi.org/10.1016/S0140-6736(10)62349-5] [PMID: 21450337 ]
[http://dx.doi.org/10.1007/s00228-017-2210-x] [PMID: 28188332 ]
[http://dx.doi.org/10.1210/jc.2016-1801] [PMID: 27270237 ]
[http://dx.doi.org/10.1056/NEJMcp1513724] [PMID: 26789873 ]
[http://dx.doi.org/10.1016/j.bone.2017.08.003] [PMID: 28789921 ]
[http://dx.doi.org/10.1126/science.3388021] [PMID: 3388021 ]
[http://dx.doi.org/10.1073/pnas.88.15.6613] [PMID: 1907373 ]
[http://dx.doi.org/10.1038/nrendo.2013.179] [PMID: 24042328 ]
[http://dx.doi.org/10.1359/jbmr.1999.14.7.1217] [PMID: 10404024 ]
[http://dx.doi.org/10.1001/jama.288.3.321] [PMID: 12117397 ]
[http://dx.doi.org/10.1001/jama.291.14.1701] [PMID: 15082697 ]
[http://dx.doi.org/10.4158/EP.16.S3.1] [PMID: 21224201 ]
[http://dx.doi.org/10.1001/jama.289.24.3243] [PMID: 12824205 ]
[http://dx.doi.org/10.7326/M15-1361] [PMID: 28492856 ]
[http://dx.doi.org/10.1152/ajpendo.00488.2015] [PMID: 27048997 ]
[http://dx.doi.org/10.1186/s40199-017-0167-z] [PMID: 28173850 ]
[http://dx.doi.org/10.1016/j.bone.2013.06.007] [PMID: 23777960 ]
[http://dx.doi.org/10.1038/bonekey.2012.67] [PMID: 23951460 ]
[http://dx.doi.org/10.1016/j.bone.2008.08.130] [PMID: 18845279 ]
[http://dx.doi.org/10.1016/j.bmcl.2007.12.047] [PMID: 18226527 ]
[http://dx.doi.org/10.1038/clpt.2009.60] [PMID: 19421185 ]
[PMID: 19874198 ]
[http://dx.doi.org/10.1016/j.coph.2016.02.012] [PMID: 26989807 ]
[http://dx.doi.org/10.1038/nrd.2016.207] [PMID: 27681784 ]
[http://dx.doi.org/10.1210/en.2009-1494] [PMID: 20501677 ]
[http://dx.doi.org/10.1074/jbc.M307444200] [PMID: 14523023 ]
[http://dx.doi.org/10.1210/jc.2011-2332] [PMID: 22238383 ]
[http://dx.doi.org/10.1056/NEJM200105103441904] [PMID: 11346808 ]
[http://dx.doi.org/10.1016/j.bone.2011.05.003] [PMID: 21600325 ]
[http://dx.doi.org/10.1210/en.2015-1726] [PMID: 26562265 ]
[http://dx.doi.org/10.1210/er.2011-1060] [PMID: 22723594 ]
[http://dx.doi.org/10.1002/jbmr.173] [PMID: 20593411 ]
[http://dx.doi.org/10.1002/jcph.239] [PMID: 24272917 ]
[http://dx.doi.org/10.1359/jbmr.060311] [PMID: 16753024 ]
[http://dx.doi.org/10.1359/jbmr.081104] [PMID: 19016584 ]
[http://dx.doi.org/10.1002/jbmr.472] [PMID: 21773994 ]
[http://dx.doi.org/10.1124/jpet.111.181404] [PMID: 21531794 ]
[http://dx.doi.org/10.1111/bjh.13056] [PMID: 25139740 ]
[http://dx.doi.org/10.1007/s00198-010-1369-0] [PMID: 20812008 ]
[PMID: 11994341 ]
[http://dx.doi.org/10.1056/NEJMoa022436] [PMID: 14749454]
[http://dx.doi.org/10.1210/jc.2004-1774] [PMID: 15728210 ]
[http://dx.doi.org/10.1007/s00198-008-0728-6] [PMID: 18763010 ]
[http://dx.doi.org/10.1111/j.1476-5381.2009.00305.x] [PMID: 19563530 ]
[http://dx.doi.org/10.1126/scisignal.135pe40] [PMID: 18765829 ]
[http://dx.doi.org/10.1210/endo.140.12.7190] [PMID: 10579354 ]
[http://dx.doi.org/10.1007/s00198-002-1343-6] [PMID: 12730784 ]
[http://dx.doi.org/10.1016/j.bbrc.2004.08.209] [PMID: 15451421 ]
[http://dx.doi.org/10.1111/j.1582-4934.2008.00673.x] [PMID: 20141614 ]
[http://dx.doi.org/10.1016/j.bcp.2007.04.020] [PMID: 17531955 ]
[http://dx.doi.org/10.1074/jbc.M110.110502] [PMID: 20554534 ]