ACTH Promotes Osteogenesis of Rat Mesenchymal Stem Cells through the Melanocortin-2 Receptor
Journal Title or Book Title
Adrenocorticotropin Hormone (ACTH) is an endocrine hormone that is secreted by the pituitary and stimulates the secretion of cortisol from the adrenal cortex. It is among the several melanocortin peptide hormones that are derived from proopiomelanocortin (POMC) such as α-melanocyte stimulating hormone (α-MSH), γ-MSH and the endorphins. ACTH is also produced by cells outside the central nervous system and has been found to play a role in osteogenesis. Using mesenchymal stem cells (MSC) obtained from bone marrow of the Wystar Kyoto (WKY) rat, we confirmed that ACTH increases osteogenesis in a dosedependent manner. Immunoblot of crude membrane fractions was used to determine that rat MSC express three melanocortin receptors (MC-R); the MC2-R, MC3-R and MC5-R. To determine which of these receptors mediate ACTH-induced osteogenesis we used MC-R specific peptides and antagonists. Neither α-MSH, a strong agonist of the MC5-R nor γ2-MSH, a strong agonist of the MC3-R, increases osteogenesis in rat MSC. Additionally the MC3-R specific antagonist did not suppress ACTH-induced increases in osteogenesis. In addition, calcium flux was examined as a mechanism for ACTH action at the MC2-R. Consistent with MC2-R expression patterns in the MSC cultures, ACTH-induced transient increases in intracellular calcium were increased with dexamethasone treatment. Therefore the osteogenic effects of ACTH in rat MSC cultures are consistent with an MC2-R signaling mechanism. This pathway represents a new therapeutic target in the prevention and treatment of bone loss.
Evans, Jodi F. Ph.D.; Rodriguez, Sylvana; and Ragolia, Louis, "ACTH Promotes Osteogenesis of Rat Mesenchymal Stem Cells through the Melanocortin-2 Receptor" (2012). Faculty Works: Biology, Chemistry, and Environmental Studies. 14.