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Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration

  • Authors:
    • Samar M. Koura
    • Mohamed Salama
    • Mahmoud El‑Hussiny
    • Mahmoud El‑Sayed Awad Khalil
    • Ahmed Lotfy
    • Samia Ahmed Hassan
    • Seham Aly Gad Elhak
    • Mohamed A. Sobh
  • View Affiliations / Copyright

    Affiliations: Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt, Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt, Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni Suef University, Beni Suef 62511, Egypt, Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
    Copyright: © Koura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2611-2619
    |
    Published online on: February 1, 2019
       https://doi.org/10.3892/mmr.2019.9924
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Abstract

Selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants worldwide, which have been reported to exert potential detrimental effects on bone mineral density and increase the risk of developing fractures. The present study aimed to investigate the pathways underlying the negative effects of fluoxetine on bone using mesenchymal stem cells (MSCs) derived from rat adipose tissue as a source of osteoprogenitor cells. MSCs were harvested from adipose tissue using a collagenase enzyme digestion method and were allowed to differentiate into osteoprogenitor cells. Various concentrations of fluoxetine were added to the cells, which were harvested and analyzed by flow cytometry to detect apoptotic markers Annexin V and caspase‑3, in order to assess the levels of apoptosis. The levels of endogenous serotonin released in the extracellular matrix were measured using a serotonin ELISA kit. The underlying molecular pathways associated with the effects of fluoxetine on bone were investigated with reverse transcription‑quantitative polymerase chain reaction. The results of the present study revealed a significant dose‑dependent increase in apoptosis in response to increasing doses of fluoxetine, which was independent of serotonin levels in the culture supernatant. These findings indicated that fluoxetine exerted a direct inhibitory effect on bone cells via an apoptosis‑dependent pathway. Furthermore, the expression levels of serotonergic genes, including serotonin 1B receptor, serotonin 2A receptor (HTR2A), serotonin 2B receptor and serotonin transporter, were down regulated; of these genes, HTR2A exhibited the highest expression levels. Further in vitro and in vivo studies are required to verify this association and to determine the molecular pathways involved in fluoxetine‑induced bone loss. Fluoxetine‑induced apoptosis of osteoprogenitor cells may be the mechanism underlying the increased incidence of bone loss observed in patients treated with fluoxetine.
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1 

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E and Bliziotes MM; Osteoporotic Fractures in Men Study Group, : Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 167:1246–1251. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Haney EM, Warden SJ and Bliziotes MM: The effects of selective serotonin reuptake inhibitors on bone health in adults: Time for recommendations about screening, prevention and management? Bone. 46:13–17. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Chen F, Hahn TJ and Weintraub NT: Do SSRIs play a role in decreasing bone mineral density? J Am Med Dir Assoc. 13:413–417. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Bliziotes MM, Eshleman AJ, Zhang XW and Wiren KM: Neurotransmitter action in osteoblasts: Expression of a functional system for serotonin receptor activation and reuptake. Bone. 29:477–486. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Westbroek I, van der Plas A, de Rooij KE, Klein-Nulend J and Nijweide PJ: Expression of serotonin receptors in bone. J Biol Chem. 276:28961–28968. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Chau K, Atkinson SA and Taylor VH: Are selective serotonin reuptake inhibitors a secondary cause of low bone density? J Osteoporos. 2012:3230612012. View Article : Google Scholar : PubMed/NCBI

7 

Bab I and Yirmiya R: Depression, selective serotonin reuptake inhibitors, and osteoporosis. Curr Osteoporos Rep. 8:185–191. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Bradaschia-Correa V, Josephson AM, Mehta D, Mizrahi M, Neibart SS, Liu C, Kennedy OD, Castillo AB, Egol KA and Leucht P: The selective serotonin reuptake inhibitor fluoxetine directly inhibits osteoblast differentiation and mineralization during fracture healing in mice. J Bone Miner Res. 32:821–833. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P and Hedrick MH: Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 13:4279–4295. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Zimmerlin L, Donnenberg VS and Donnenberg AD: Rare event detection and analysis in flow cytometry: Bone marrow mesenchymal stem cells, breast cancer stem/progenitor cells in malignant effusions, and pericytes in disaggregated adipose tissue. Methods Mol Biol. 699:251–273. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Halvorsen YD, Franklin D, Bond AL, Hitt DC, Auchter C, Boskey AL, Paschalis EP, Wilkison WO and Gimble JM: Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng. 7:729–741. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Salamh M, Mehanna R, Hanafy Sh and Abdel Ghafar H: The usage of liver extract verses growth factors in the differentiation of mesenchymal stem cells into hepatocyte like cells. J Int Acad Res Multidisciplinary. 2:35–50. 2014.

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Dale E, Bang-Andersen B and Sánchez C: Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochem Pharmacol. 95:81–97. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Tsapakis EM, Gamie Z, Tran GT, Adshead S, Lampard A, Mantalaris A and Tsiridi E: The adverse skeletal effects of selective serotonin reuptake inhibitors. Eur Psychiatry. 27:156–169. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Hodge JM, Wang Y, Berk M, Collier FM, Fernandes TJ, Constable MJ, Pasco JA, Dodd S, Nicholson GC, Kennedy RL and Williams LJ: Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biol Psychiatry. 74:32–39. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Ortuño MJ, Robinson ST, Subramanyam P, Paone R, Huang YY, Guo XE, Colecraft HM, Mann JJ and Ducy P: Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat Med. 22:1170–1179. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Schaz U, Föhr KJ, Liebau S, Fulda S, Koelch M, Fegert JM, Boeckers TM and Ludolph AG: Dose-dependent modulation of apoptotic processes by fluoxetine in maturing neuronal cells: An in vitro study. World J Biol Psychiatry. 12:89–98. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Rafiei M, Sadeghian S, Torabinia N and Hajhashemi V: Systemic effects of fluoxetine on the amount of tooth movement, root resorption, and alveolar bone remodeling during orthodontic force application in rat. Dent Res J (Isfahan). 12:482–487. 2017.

20 

Gustafsson BI, Westbroek I, Waarsing JH, Waldum H, Solligård E, Brunsvik A, Dimmen S, van Leeuwen JP, Weinans H and Syversen U: Long-term serotonin administration leads to higher bone mineral density, affects bone architecture, and leads to higher femoral bone stiffness in rats. J Cell Biochem. 97:1283–1291. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Dai SQ, Yu LP, Shi X, Wu H, Shao P, Yin GY and Wei YZ: Serotonin regulates osteoblast proliferation and function in vitro. Braz J Med Biol Res. 47:759–765. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Nam SS, Lee JC, Kim HJ, Park JW, Lee JM, Suh JY, Ums HS, Kim JY, Lee Y and Kim YG: Serotonin inhibits osteoblast differentiation and bone regeneration in rats. J Periodontol. 87:461–469. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Battaglino R, Vokes M, Schulze-Späte U, Sharma A, Graves D, Kohler T, Müller R, Yoganathan S and Stashenko P: Fluoxetine treatment increases trabecular bone formation in mice. J Cell Biochem. 100:1387–1394. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Mortazavi SH, Khojasteh A, Vaziri H, Khoshzaban A, Roudsari MV and Razavi SH: The effect of fluoxetine on bone regeneration in rat calvarial bone defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 108:22–27. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Koura SM, Salama M, El‑Hussiny M, Khalil ME, Lotfy A, Hassan SA, Gad Elhak SA and Sobh MA: Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration. Mol Med Rep 19: 2611-2619, 2019.
APA
Koura, S.M., Salama, M., El‑Hussiny, M., Khalil, M.E., Lotfy, A., Hassan, S.A. ... Sobh, M.A. (2019). Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration. Molecular Medicine Reports, 19, 2611-2619. https://doi.org/10.3892/mmr.2019.9924
MLA
Koura, S. M., Salama, M., El‑Hussiny, M., Khalil, M. E., Lotfy, A., Hassan, S. A., Gad Elhak, S. A., Sobh, M. A."Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration". Molecular Medicine Reports 19.4 (2019): 2611-2619.
Chicago
Koura, S. M., Salama, M., El‑Hussiny, M., Khalil, M. E., Lotfy, A., Hassan, S. A., Gad Elhak, S. A., Sobh, M. A."Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration". Molecular Medicine Reports 19, no. 4 (2019): 2611-2619. https://doi.org/10.3892/mmr.2019.9924
Copy and paste a formatted citation
x
Spandidos Publications style
Koura SM, Salama M, El‑Hussiny M, Khalil ME, Lotfy A, Hassan SA, Gad Elhak SA and Sobh MA: Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration. Mol Med Rep 19: 2611-2619, 2019.
APA
Koura, S.M., Salama, M., El‑Hussiny, M., Khalil, M.E., Lotfy, A., Hassan, S.A. ... Sobh, M.A. (2019). Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration. Molecular Medicine Reports, 19, 2611-2619. https://doi.org/10.3892/mmr.2019.9924
MLA
Koura, S. M., Salama, M., El‑Hussiny, M., Khalil, M. E., Lotfy, A., Hassan, S. A., Gad Elhak, S. A., Sobh, M. A."Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration". Molecular Medicine Reports 19.4 (2019): 2611-2619.
Chicago
Koura, S. M., Salama, M., El‑Hussiny, M., Khalil, M. E., Lotfy, A., Hassan, S. A., Gad Elhak, S. A., Sobh, M. A."Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration". Molecular Medicine Reports 19, no. 4 (2019): 2611-2619. https://doi.org/10.3892/mmr.2019.9924
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