{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T13:32:19Z","timestamp":1777728739817,"version":"3.51.4"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>5-HTT mediates antidepressant-sensitive clearance of 5-HT after its release into neural synapses. We found increased expression of 5-HTT in RANKL-induced osteoclast-like cells. Fluoxetine, an inhibitor of 5-HTT, reduced osteoclast differentiation but not activation. Reserpine, an inhibitor of 5-HT intracellular transport, potentiated differentiation. These results indicate a role for 5-HTT in osteoclast function and suggest that commonly used antidepressive agents may affect bone mass.<\/jats:p>\n               <jats:p>Introduction: Interactions between the serotonergic and skeletal systems are suggested by various clinical observations but are poorly understood.<\/jats:p>\n               <jats:p>Materials and Methods: Using gene microarrays, we found that the serotonin transporter (5-HTT) was strongly expressed in RANKL-induced osteoclasts. Using RANKL stimulation of RAW264.7 cells and mouse bone marrow cells as a model system for osteoclast differentiation, we studied the possible role\/s of the different components of the serotonin (5-HT) system on the differentiation process.<\/jats:p>\n               <jats:p>Results: Osteoclast 5-HTT exhibited typical 5-HT uptake activity that was inhibitable by fluoxetine (Prozac). Fluoxetine reduced osteoclast differentiation but did not inhibit the activation of preformed osteoclasts, whereas the addition of 5-HT itself enhanced differentiation. Fluoxetine-treated osteoclast precursors had reduced NF-\u03baB activation and elevated inhibitory protein \u03baB\u03b1 (I\u03baB\u03b1) levels compared with untreated cells. 5-HT, on the other hand, resulted in activation of NF-\u03baB. Reserpine inhibition of intracellular transport of 5-HT into cytoplasmic vesicles potentiated RANKL-induced osteoclast formation, suggesting the importance of intracellular 5-HT in regulating osteoclast differentiation. Reserpine also modestly enhanced the expression of the osteoclast marker TRACP in the absence of RANKL.<\/jats:p>\n               <jats:p>Conclusions: Taken together, these data suggest that the 5-HT system plays an important role in bone homeostasis through effects on osteoclast differentiation and implies that commonly used antidepressive agents may affect bone mass.<\/jats:p>","DOI":"10.1359\/jbmr.040606","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T08:40:56Z","timestamp":1146127256000},"page":"1420-1431","source":"Crossref","is-referenced-by-count":176,"title":["Serotonin Regulates Osteoclast Differentiation Through Its Transporter"],"prefix":"10.1093","volume":"19","author":[{"given":"Ricardo","family":"Battaglino","sequence":"first","affiliation":[{"name":"Department of Cytokine Biology, The Forsyth Institute, Boston, Massachusetts, USA"}]},{"given":"Jia","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cytokine 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