OR2H2 regulates the differentiation of human myoblast cells by its ligand aldehyde 13-13.

Olfactory receptors (ORs) regulate various cellular processes in the human body. The receptors' participation in physiological and pathophysiological processes could be demonstrated in several studies. In addition to the regulation of sperm motility, respiratory physiology, and heart contraction, ORs play a crucial role in cancer cells. In murine myoblasts, mOR23 regulates the myogenesis and branching of skeletal muscle cells. To date, the expression and physiological role of ORs in human skeletal muscle cells have not been thoroughly elucidated. We demonstrate that four different ORs are expressed at the transcript level in differentiated myoblasts, and one other OR is expressed in undifferentiated myoblasts. Moreover, we characterized the expression of OR2H2 in differentiated human myoblasts and identified a specific ligand, aldehyde 13-13. We could observe a concentration-dependent Ca2+ increase in differentiated human myoblasts upon aldehyde 13-13 stimulation, which is mediated by PI3K signaling. Aldehyde 13-13 has a reducing effect on myoblast fusion. We conclude that OR2H2 could have a regulatory role in myoblast differentiation. To the best of our knowledge, this report presents the first verification of the expression of ORs in human myoblasts. OR2H2 might be an interesting candidate for playing a role in the complex mechanism of myogenesis.

Olfactory Receptors Modulate Physiological Processes in Human Airway Smooth Muscle Cells.

Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies, key pathological mechanisms, and putative clinical targets need to be identified. In the present study, we demonstrated that the human olfactory receptors (ORs) OR1D2 and OR2AG1 are expressed at the RNA and protein levels in HASMCs. Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca(2+) increases in HASMCs via a cAMP-dependent signal transduction cascade. Furthermore, the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of HASMCs, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility. In addition, OR1D2 activation induced the secretion of IL-8 and GM-CSF. Both effects were inhibited by the specific OR1D2 antagonist undecanal. We herein provide the first evidence to show that ORs are functionally expressed in HASMCs and regulate pathophysiological processes. Therefore, ORs might be new therapeutic targets for these diseases, and blocking ORs could be an auspicious strategy for the treatment of early-stage chronic inflammatory lung diseases.