Inhibition of the Serotonin (5-Hydroxytryptamine) Transporter Reduces Bone Accrual during Growth

Author:

Warden Stuart J.12,Robling Alexander G.3,Sanders Megan S.1,Bliziotes Michael M.45,Turner Charles H.16

Affiliation:

1. Department of Orthopaedic Surgery (S.J.W., M.S.S., C.H.T.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202

2. Indiana University School of Medicine, and Department of Physical Therapy (S.J.W.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202

3. Department of Anatomy and Cell Biology (A.G.R.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202

4. Portland Veteran Affairs Medical Center (M.M.B.), Portland, Oregon 97201

5. Oregon Health and Science University (M.M.B.), Portland Oregon 97239

6. Biomechanics and Biomaterials Research Center (C.H.T.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202

Abstract

Abstract Selective serotonin-reuptake inhibitors (SSRIs) antagonize the serotonin (5-hydroxytryptamine) transporter (5-HTT), and are frequently prescribed to children and adolescents to treat depression. However, recent findings of functional serotonergic pathways in bone cells and preliminary clinical evidence demonstrating detrimental effects of SSRIs on bone growth have raised questions regarding the effects of these drugs on the growing skeleton. The current work investigated the impact of 5-HTT inhibition on the skeleton in: 1) mice with a null mutation in the gene encoding for the 5-HTT; and 2) growing mice treated with a SSRI. In both models, 5-HTT inhibition had significant detrimental effects on bone mineral accrual. 5-HTT null mutant mice had a consistent skeletal phenotype of reduced mass, altered architecture, and inferior mechanical properties, whereas bone mineral accrual was impaired in growing mice treated with a SSRI. These phenotypes resulted from a reduction in bone formation without an increase in bone resorption and were not influenced by effects on skeletal mechanosensitivity or serum biochemistries. These findings indicate a role for the 5-HTT in the regulation of bone accrual in the growing skeleton and point to a need for further research into the prescription of SSRIs to children and adolescents.

Publisher

The Endocrine Society

Subject

Endocrinology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3