Expression of serotonin receptors in bone

Abstract The 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, and 5-HT2Cbelong to a subfamily of serotonin receptors. Amino acid and mRNA sequences of these receptors have been published for several species including man. The 5-HT2 receptors have been reported to act on nervous, muscle, and endothelial tissues. Here we report the presence of 5-HT2B receptor in fetal chicken bone cells. 5-HT2B receptor mRNA expression was demonstrated in osteocytes, osteoblasts, and periosteal fibroblasts, a population containing osteoblast precursor cells. Pharmacological studies using several agonists and antagonists showed that occupancy of the 5-HT2B receptor stimulates the proliferation of periosteal fibroblasts. Activity of the 5-HT2A receptor could however not be excluded. mRNA for both receptors was shown to be equally present in adult mouse osteoblasts. Osteocytes, which showed the highest expression of 5-HT2B receptor mRNA in chicken, and to a lesser extent osteoblasts, are considered to be mechanosensor cells involved in the adaptation of bone to its mechanical usage. Nitric oxide is one of the signaling molecules that is released upon mechanical stimulation of osteocytes and osteoblasts. The serotonin analog α-methyl-5-HT, which preferentially binds to 5-HT2 receptors, decreased nitric oxide release by mechanically stimulated mouse osteoblasts. These results demonstrate that serotonin is involved in bone metabolism and its mechanoregulation.