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

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

Author information

1
Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil.
2
Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Faro 8005-139, Portugal.
3
Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil; Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Faro 8005-139, Portugal. Electronic address: 00107953@ufrgs.br.

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

PMID:
25591908
DOI:
10.1016/j.mce.2015.01.010
[Indexed for MEDLINE]
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