title: STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition.
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.
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil.
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Terra
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Faro 8005-139, Portugal.
authors.forename: João Carlos R
authors.initials: JC
authors.lastname: Cardoso
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Faro 8005-139, Portugal.
authors.forename: Rute C
authors.initials: RC
authors.lastname: Félix
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil.
authors.forename: Leo Anderson M
authors.initials: LA
authors.lastname: Martins
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil.
authors.forename: Diogo Onofre G
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90003-035, Brazil.
authors.forename: Fatima C R
authors.initials: FC
authors.lastname: Guma
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Faro 8005-139, Portugal.
authors.forename: Adelino Vicente M
authors.initials: AV
authors.lastname: Canário
authors.affiliation: 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Schein
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055503:Protein Multimerization; D058262:Receptor Activity-Modifying Protein 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D006023:Glycoproteins; C545502:RAMP1 protein, human; D058262:Receptor Activity-Modifying Protein 1; D005576:Colforsin; C051795:teleocalcin; D002116:Calcitonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide
keywords: Calcitonin gene-related peptide; Calcitonin gene-related peptide receptor; Osteoblastogenesis; Stanniocalcin 1; cAMP