Serotonin On Osteoblast Proliferation, Differentiation And Mineralization Features And The Effects Of Parameters On The Mice Bone

【Background】 The monoamine serotonin (5-hydroxytryptamine,5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system.Clinical observations and several studies have suggested that serotonin is involved inbone metabolism. However, conflicting results about the effects of serotonin have beenreported. The objectives of this study were to investigate the role of serotonin in theproliferation and function of osteoblasts, to analyze the expression of serotonin receptorsubtypes in osteoblasts at different stages of differentiation, and to study the effect ofserotonin on in vivo bone metabolism in rodents.【Methods】 We treated rat primarycalvarial osteoblasts with various concentrations of serotonin (10-9mol/L-10-5mol/L) andassessed the rate of osteoblast proliferation, expression levels of osteoblast-specificproteins and their respective genes, and the ability to form mineralized nodules. Next, wedetected which5-HT receptor subtypes were expressed in rat osteoblasts at differentstages of osteoblast differentiation via qRT-PCR. We also determined bone mass andbone microarchitecture of female mice injected with different doses of serotonin for threemonths by micro-computed tomography.【Results】 We found that serotonin couldinhibit osteoblast proliferation, differentiation, and mineralization in a dose-dependentmanner at low concentrations, but this inhibitory effect was mitigated at highconcentrations. All six of the5-hydroxytryptamine (5-HT) receptor subtypes—5-HT1A,5-HT1B,5-HT1D,5-HT2A,5-HT2B, and5-HT2C—were found in rat osteoblasts. Of these,5-HT2Aand5-HT1Breceptors had the highest expression levels, at both early and latestages of differentiation. Systemic administration of serotonin to female mice resulted insignificantly decreased bone mass and altered microarchitecture in both trabecular andcortical bones, as determined by micro-computed tomography.【Conclusion】 Ourresults indicate that serotonin does indeed have a significant regulatory effect on bonemetabolism both in vitro and in vivo. The cause of dual effects of serotonin on bone metabolism may rely on the different signaling pathways of different serotonin receptorsubtypes. This may be a promising new target for the prevention and treatment of boneloss–associated disorders such as osteoporosis.