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

Mol Cell Endocrinol. 2015 Mar 5;403:78-87. doi: 10.1016/j.mce.2015.01.010. Epub 2015 Jan 12.

Abstract

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.

Keywords: Calcitonin gene-related peptide; Calcitonin gene-related peptide receptor; Osteoblastogenesis; Stanniocalcin 1; cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / genetics*
  • Adenylyl Cyclases / metabolism
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Calcitonin / pharmacology
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Receptor-Like Protein / genetics*
  • Calcitonin Receptor-Like Protein / metabolism
  • 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
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Protein Multimerization
  • Receptor Activity-Modifying Protein 1 / genetics
  • Receptor Activity-Modifying Protein 1 / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Adenylyl Cyclase Inhibitors
  • CALCRL protein, human
  • Calcitonin Receptor-Like Protein
  • Glycoproteins
  • RAMP1 protein, human
  • Receptor Activity-Modifying Protein 1
  • Colforsin
  • teleocalcin
  • Calcitonin
  • Cyclic AMP
  • Adenylyl Cyclases
  • Calcitonin Gene-Related Peptide