Expression of serotonin receptors in bone

The 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, and 5-HT2C belong to a subfamily of serotonin receptors. Amino acid and mRNA sequences of the se receptors have been published for several species including man. The 5-H T2 receptors have been reported to act on nervous, muscle, and endothelial tissues. Here we report the presence of 5-HT2B receptor in fetal chicken bo ne cells. 5-HT2B receptor mRNA expression was demonstrated in osteocytes, o steoblasts, and periosteal fibroblasts, a population containing osteoblast precursor cells. Pharmacological studies using several agonists and antagon ists showed that occupancy of the 5-HT2. receptor stimulates the proliferat ion of periosteal fibroblasts. Activity of the 5-HT2A receptor could howeve r 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, ar e considered to be mechanosensor cells involved in the adaptation of bone t o its mechanical usage. Nitric oxide is one of the signaling molecules that is released upon mechanical stimulation of osteocytes and osteoblasts. The serotonin analog alpha -methyl-5-HT, which preferentially binds to 5-HT2 r eceptors, decreased nitric oxide release by mechanically stimulated mouse o steoblasts. These results demonstrate that serotonin is involved in bone me tabolism and its mechanoregulation.