STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition

• Published in: Molecular and cellular endocrinology 2015-03, Vol.403, p.78-87
• Main Authors: Terra, Silvia R., Cardoso, João Carlos R., Félix, Rute C., Martins, Leo Anderson M., Souza, Diogo Onofre G., Guma, Fatima C.R., Canário, Adelino Vicente M., Schein, Vanessa
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Calcitonin - pharmacology; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - pharmacology; Calcitonin gene-related peptide receptor; Calcitonin Receptor-Like Protein - genetics; Calcitonin Receptor-Like Protein - metabolism; cAMP; Cell Differentiation; Cell Membrane - chemistry; Cell Membrane - drug effects; Cell Membrane - metabolism; Colforsin - pharmacology; Cyclic AMP - metabolism; Gene Expression Regulation; Glycoproteins - metabolism; Glycoproteins - pharmacology; HEK293 Cells; Humans; Osteoblastogenesis; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Protein Multimerization; Receptor Activity-Modifying Protein 1 - genetics; Receptor Activity-Modifying Protein 1 - metabolism; Signal Transduction; Stanniocalcin 1; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.01.010

•hSTC1 is a cAMP signaling inhibitor.•hSTC1 and hCGRP peptides activate distinct signaling pathways.•hSTC1 promotes CGRP receptor assembly during osteoblastogenesis.•hSTC1 in vivo inhibits hCT, but not hCGRP, cAMP signaling. Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation.