5-羟色胺选择性重摄取抑制剂对骨代谢的影响及机制

周丽敏; 徐永祥

doi:10.6039/j.issn.1001-0408.2023.23.20

您当前的位置：

首页 >

文章列表页 >

5-羟色胺选择性重摄取抑制剂对骨代谢的影响及机制

综述 | 更新时间：2023-12-08

- 5-羟色胺选择性重摄取抑制剂对骨代谢的影响及机制
- Effect and mechanism of serotonin-selective reuptake inhibitor on bone metabolism
- 中国药房 2023年34卷第23期页码：2928-2933
- 作者机构：
  
  东莞市人民医院药学部，广东东莞　523059
- 作者简介：
  
  药师，硕士。研究方向：骨药理学。E-mail：553858122@qq.com
  副主任药师，硕士生导师，硕士。研究方向：骨药理学。E-mail：61648235@163.com
- 基金信息：
  
  广东省基础与应用基础研究基金项目(2021B1515140054);东莞市社会科技发展（重点）项目(202050715001197)
- DOI：10.6039/j.issn.1001-0408.2023.23.20
  中图分类号： R971+.43;R336
- 纸质出版日期：2023-12-15，
  
  收稿日期：2023-05-17，
  
  修回日期：2023-11-15，
扫描看全文
周丽敏,徐永祥.5-羟色胺选择性重摄取抑制剂对骨代谢的影响及机制 ^Δ[J].中国药房,2023,34(23):2928-2933.

ZHOU Limin,XU Yongxiang.Effect and mechanism of serotonin-selective reuptake inhibitor on bone metabolism[J].ZHONGGUO YAOFANG,2023,34(23):2928-2933.
周丽敏,徐永祥.5-羟色胺选择性重摄取抑制剂对骨代谢的影响及机制 ^Δ[J].中国药房,2023,34(23):2928-2933. DOI： 10.6039/j.issn.1001-0408.2023.23.20.

ZHOU Limin,XU Yongxiang.Effect and mechanism of serotonin-selective reuptake inhibitor on bone metabolism[J].ZHONGGUO YAOFANG,2023,34(23):2928-2933. DOI： 10.6039/j.issn.1001-0408.2023.23.20.

摘要

5-羟色胺选择性重摄取抑制剂（SSRI）是治疗抑郁症的一线药物，主要包括氟西汀、帕罗西汀、舍曲林、氟伏沙明、西酞普兰、艾司西酞普兰等。SSRI对骨代谢具有双重影响，短期使用可能会对骨骼有积极影响，但若长期使用可能导致骨骼问题。本文总结了SSRI对骨代谢的影响及其机制，可知SSRI能影响骨形成、骨吸收、间充质干细胞分化以及调节炎症细胞因子表达，并通过cAMP/PKA/CREB、Wnt/

-catenin、BMP/Smad、OPG/RANKL/RANK等经典信号通路以及中枢介导作用影响骨代谢。

Abstract

erotonin-selective reuptake inhibitor （SSRI） is the first-line drug for treating depression. SSRI mainly include fluoxetine， paroxetine， sertraline， fluvoxamine， citalopram and escitalopram， etc. SSRI has dual impact on bone metabolism. Short-term use of SSRI may have a positive impact on bone， but long-term use may lead to bone problems. This article summarizes the effects and mechanisms of SSRI on bone metabolism， indicating that SSRI can affect bone formation， bone resorption， mesenchymal stem cell differentiation， and regulate the expression of inflammatory cytokines. The impact of SSRI on bone metabolism can be achieved by affecting classical signaling pathways such as cAMP/PKA/CREB， Wnt/

-catenin， BMP/Smad， OPG/RANKL/RANK， and through centrally mediated effects.

关键词

5-羟色胺选择性重摄取抑制剂骨代谢机制信号通路骨形成骨吸收间充质干细胞分化炎症细胞因子

Keywords

bone metabolismmechanismsignaling pathwaybone formationbone resorptiondifferentiation of mesenchymal stem cellinflammatory cytokine

references

LAVOIE B，LIAN J B，MAWE G M. Regulation of bone metabolism by serotonin[J]. Adv Exp Med Biol，2017，1033：35-46.

WADHWA R，KUMAR M，TALEGAONKAR S，et al. Serotonin reuptake inhibitors and bone health：a review of clinical studies and plausible mechanisms[J]. Osteoporos Sarcopenia，2017，3（2）：75-81.

MAWE G M，HOFFMAN J M. Serotonin signalling in the gut：functions，dysfunctions and therapeutic targets[J]. Nat Rev Gastroenterol Hepatol，2013，10（8）：473-486.

WEERASINGHE D K，HODGE J M，PASCO J A，et al. Antipsychotic-induced bone loss：the role of dopamine，serotonin and adrenergic receptor signalling[J]. Front Cell Dev Biol，2023，11：1184550.

MERCURIO M，FILIPPIS R D，SPINA G，et al. The use of antidepressants is linked to bone loss：a systematic review and metanalysis[J]. Orthop Rev，2022，14（6）：38564.

FILIPPIS R D，MERCURIO M，SPINA G，et al. Antidepressants and vertebral and hip risk fracture：an updated systematic review and meta-analysis[J]. Healthcare，2022，10（5）：803.

PIRKLE S，BHATTACHARJEE S，DAFRAWY M E， et al. The influence of selective serotonin reuptake inhibitors on lumbar arthrodesis[J]. Clin Spine Surg，2021，34（4）：E200-E204.

SÁNCHEZ N，JUÁREZ-BALAREZO J，OLHABERRY M，et al. Depression and antidepressants during pregnancy：craniofacial defects due to stem/progenitor cell deregulation mediated by serotonin[J]. Front Cell Dev Biol，2021，9：632766.

LAM R W，WONG H K，KUMARSING R A，et al. Fluo- xetine improves bone microarchitecture and mechanical properties in rodents undergoing chronic mild stress：an animal model of depression[J]. Transl Psychiatry，2022，12（1）：339.

HO R C，CHUA A N，HUSAIN S F，et al. Premenopausal Singaporean women suffering from major depressive disorder treated with selective serotonin reuptake inhibitors had similar bone mineral density as compared with healthy controls[J]. Diagnostics，2022，12（1）：96.

赵芳冰，申晓青. 选择性5-羟色胺再摄取抑制剂对骨代谢影响的研究进展[J]. 医学研究生学报，2021，34（6）：653-657.

ZHAO F B，SHEN X Q. Research progress on the effect of selective 5-hydroxytryptamine serotonin reuptake inhibitors on bone metabolism[J]. J Med Postgrad，2021，34（6）：653-657.

BRADASCHIA-CORREA V，JOSEPHSON A M，MEHTA D，et al. The selective serotonin reuptake inhibitor fluo- xetine directly inhibits osteoblast differentiation and mineralization during fracture healing in mice[J]. J Bone Miner Res，2017，32（4）：821-833.

LEE S，REMARK L H，BUCHALTER D B，et al. Propranolol reverses impaired fracture healing response observed with selective serotonin reuptake inhibitor treatment[J]. J Bone Miner Res，2020，35（5）：932-941.

GAO H，HUANG J M，WEI Q，et al. Advances in animal models for studying bone fracture healing[J]. Bioenginee- ring，2023，10（2）：201.

HOWIE R N，HERBERG S，DURHAM E，et al. Selective serotonin reuptake inhibitor sertraline inhibits bone hea- ling in a calvarial defect model[J]. Int J Oral Sci，2018，10（3）：25.

SALAI M，SOMJEN D，GIGI R，et al. Effects of commonly used medications on bone tissue mineralisation in SaOS-2 human bone cell line：an in vitro study[J]. Bone Joint J，2013，95-B（11）：1575-1580.

DUCY P，KARSENTY G. The two faces of serotonin in bone biology[J]. J Cell Biol，2010，191（1）：7-13.

KUMAR M，WADHWA R，KOTHARI P，et al. Differential effects of serotonin reuptake inhibitors fluoxetine and escitalopram on bone markers and microarchitecture in Wistar rats[J]. Eur J Pharmacol，2018，825：57-62.

WADHWA R，KUMAR M，PAUDEL Y N，et al. Effect of escitalopram and carbidopa on bone markers in Wistar rats：a preliminary experimental study[J]. J Bone Miner Metab，2019，37（1）：36-42.

KUMAR M，JILOHA R C，KATARIA D，et al. Effect of selective serotonin reuptake inhibitors on markers of bone loss[J]. Psychiatry Res，2019，276：39-44.

MIYAMOTO K，OHKAWARA B，ITO M，et al. Fluo- xetine ameliorates cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling[J]. PLoS One，2017，12（9）：e0184388.

TUNC-OZCAN E，BROOKER S M，BONDS J A，et al. Hippocampal BMP signaling as a common pathway for antidepressant action[J]. Cell Mol Life Sci，2021，79（1）：31.

TACHI J，ONUMA T，YAMAGUCHI S，et al. Duloxetine suppresses BMP-4-induced release of osteoprotegerin via inhibition of the SMAD signaling pathway in osteoblasts[J]. Biochim Biol Cell，2021，99（5）：578-586.

DURHAM E，ZHANG Y H，LARUE A，et al. Selective serotonin reuptake inhibitors （SSRI） affect murine bone lineage cells[J]. Life Sci，2020，255：117827.

ORTUÑO M J，ROBINSON S T，SUBRAMANYAM P，et al. Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect[J]. Nat Med，2016，22（10）：1170-1179.

SIMS N A，MARTIN T J. Osteoclasts provide coupling signals to osteoblast lineage cells through multiple mechanisms[J]. Annu Rev Physiol，2020，82：507-529.

SHAFIEY S I，MOHAMED W R，ABO-SAIF A A. Paro- xetine and rivastigmine mitigates adjuvant-induced rheumatoid arthritis in rats：impact on oxidative stress，apoptosis and RANKL/OPG signals[J]. Life Sci，2018，212：109-118.

SHEFTEL C M，SARTORI L C，HUNT E R，et al. Peripartal treatment with low-dose sertraline accelerates mammary gland involution and has minimal effects on maternal and offspring bone[J]. Physiol Rep，2022，10（5）：e15204.

ZHANG H L，LI K F，ZHAO Y N，et al. Long-term use of fluoxetine accelerates bone loss through the disruption of sphingolipids metabolism in bone marrow adipose tissue[J]. Transl Psychiatry，2020，10（1）：138.

KOURA S M，SALAMA M，EL-HUSSINY M，et al. Fluoxetine induces direct inhibitory effects on mesenchymal stem cell-derived osteoprogenitor cells independent of serotonin concentration[J]. Mol Med Rep，2019，19（4）：2611-2619.

KHADEMI M，TAGHIZADEH GHAVAMABADI R，TAGHAVI M M，et al. The effects of fluoxetine on the human adipose-derived stem cell proliferation and differentiation[J]. Fundam Clin Pharmacol，2019，33（3）：286-295.

FERRONI L，GARDIN C，BELLIN G，et al. Effects of novel antidepressant drugs on mesenchymal stem cell physiology[J]. Biomedecine Pharmacother，2019，114：108853.

JAMES A W. Review of signaling pathways governing MSC osteogenic and adipogenic differentiation[J]. Scientifica，2013，2013：684736.

KRUK J S，BERMEO S，SKARRATT K K，et al. The effect of antidepressants on mesenchymal stem cell differentiation[J]. J Bone Metab，2018，25（1）：43-51.

ABU NADA L，SUBAIE A A，MANSOUR A，et al. The antidepressant drug，sertraline，hinders bone healing and osseointegration in rats’ tibiae[J]. J Clin Periodontol，2018，45（12）：1485-1497.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

中药单体及复方干预Wnt信号通路调控骨代谢的研究进展