ACTH promotes chondrogenic nodule formation and induces transient elevations in intracellular calcium in rat bone marrow cell cultures via MC2-R signaling

作者：Evans Jodi F; Rodriguez Sylvana; Ragolia Louis^*

来源：Cell and Tissue Research, 2013, 352(2): 413-425.

DOI：10.1007/s00441-013-1561-6

• Proopiomelanocortin
• Adrenocorticotropic hormone
• Osteogenesis
• Chondrogenesis
• Mesenchymal progenitors
• Prohormone convertases
• beta-Lipotropic hormone (beta-LPH)
• Rat (Wistar Kyoto)

Adrenocorticotropic hormone (ACTH) is among several melanocortin peptide hormones that are derived from proopiomelanocortin (POMC). ACTH has been found to enhance osteogenesis and chondrogenesis. We show that, in the presence of dexamethasone, ACTH dose-dependently increases chondrogenic nodule formation in bone marrow stromal cells (BMSC) from the Wistar Kyoto (WKY) rat. The nodules consist in condensed cells highly expressing alkaline phosphatase, Sox9 and type II collagen transcripts and a proteoglycan-rich matrix. Immunoblot analysis of crude membrane fractions has shown that these cells express three melanocortin receptors (MC-R), namely MC2-R, MC3-R and MC5-R and the melanocortin 2-receptor accessory protein (MRAP). To determine which of these receptors mediate ACTH-induced effects, we have used MC-R-specific peptides and the known agonist profiles of the receptors. Neither alpha-MSH, a strong agonist of MC5-R, nor gamma(2)-MSH, a strong agonist of MC3-R, duplicates ACTH effects in rat BMSC. In addition, calcium flux has been examined as a mechanism for ACTH action at the MC2-R. Consistent with MC2-R and MRAP expression patterns in the BMSC cultures, ACTH-induced transient increases in intracellular calcium are increased with dexamethasone treatment. Neither alpha-MSH nor gamma(2)-MSH affects calcium flux. Dexamethasone increases MC2-R and MRAP expression and POMC peptide expression and cleavage increasing the production of the lipolytic beta-lipotropic hormone product. Therefore, the effects of ACTH in rat BMSC enriched for mesenchymal progenitors are consistent with an MC2-R signaling mechanism, with dexamethasone being capable of regulating components of the melanocortin system in these cells.

• 出版日期2013-5