Expression of Serotonin Receptors in Bone

Abstract

The 5-hydroxytryptamine (5-HT) receptors 5-HT 2A , 5-HT 2B , and 5-HT 2C belong to a subfamily of serotonin receptors. Amino acid and mRNA sequences of these receptors have been published for several species including man. The 5-HT 2 receptors have been reported to act on nervous, muscle, and endothelial tissues. Here we report the presence of 5-HT 2B receptor in fetal chicken bone cells. 5-HT 2B 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-HT 2B receptor stimulates the proliferation of periosteal fibroblasts. Activity of the 5-HT 2A 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-HT 2B 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 ␣-methyl-5-HT, which preferentially binds to 5-HT 2 receptors, decreased nitric oxide release by mechanically stimulated mouse osteoblasts. These results demonstrate that serotonin is involved in bone metabolism and its mechanoregulation.The main highly differentiated cell types in bone tissue are the osteoclast, the osteoblast (OB), 1 and the osteocyte (OCY). Osteoclasts are multinucleated cells of hemopoietic origin and are related to the monocyte/macrophage (1, 2, 3). Osteoblasts on the other hand are of mesenchymal stock. Their stem and progenitor cells are present in the periosteum, endosteum, and bone marrow stroma (4). Osteocytes differentiate from osteoblasts. During the process of bone formation, a number of cells from the osteoblast layer is encapsulated in the newly formed bone matrix, whereas the other cells retract with the bone formation front. The cells that are incorporated in the bone matrix change from a cuboidal into a more stellate-shaped morphology and become osteocytes. The result of this process is a three-dimensional cellular network of osteocytes within the mineralized matrix connected to each other and to the bone surface cells by thin cell processes (5).Together these three cell types produce, maintain, and adapt or repair, if necessary, the mineralized bone matrix. Osteoclasts are capable of bone resorption, osteoblasts of bone formation. The function of osteocytes is less well understood. Because of their location within the bone matrix, osteocytes are in a prime position for the detection of mechanical inadequacies of the tissue. They are believed to act as sensor cells that translate mechanical stimuli resulting from gravitational and muscular forces on the skeleton into biochemical signals. These biochemical signals in turn activate the effectors of bone turnover, osteoclasts...

Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells

“…This is the first report of 5-HTT expression in osteocytes, and extends our previous observations of 5-HTT and 5-HT receptor expression in osteoblasts [23]. Previously, 5-HT 2B receptor mRNA expression was reported in osteocytes [22]. We have also demonstrated 5-HT stimulation of PGE 2 levels in MLO-Y4 cells.…”

“…Augmentation of synaptic activity by inhibition of sodium-dependent monoamine transport forms the basis for the mechanism of action of important antidepressant drugs. [22] demonstrated the expression of mRNA for the serotonin (5-HT) 2B receptor in chicken osteocytes, osteoblasts, and periosteal fibroblasts, a population containing osteoblast precursor cells. In addition, they found mRNA expression for the 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in murine osteoblasts.…”

Possible mechanisms for the skeletal effects of antipsychotics in children and adolescents

“…A number of functional serotonin receptors [e.g. 5-hydroxytryptamine 1A (5-HT 1A ), 5-HT 1B , 5-HT 2A , 5-HT 2B ] along with the serotonin transporter have been identified in bone cells [Bliziotes et al 2001;Westbroek et al 2001;Yadav et al 2008]. This has recently stimulated great interest in understanding the role of serotonin in bone metabolism .…”

Expression of mRNA for 5-HT2 Receptors and Proteins Related to Inactivation of 5-HT in Mouse Osteoblasts

“…Westbroek et al (13) reported that the 5-HT 2B receptor plays a role in the modulation of the mechanosensory function of osteocytes. Recently, Collet et al (2008) reported that female 5-HT 2B -receptor knockout mice displayed a reduction in bone density that was significant from age 4 months (14).…”