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
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.
Mol Cell Endocrinol. 2015 Mar 5;403:78-87. doi: 10.1016/j.mce.2015.01.010. Epub 2015 Jan 12.
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.
鲽源钙调蛋白1（STC1）和降钙素基因相关肽（CGRP）参与骨形成/重塑过程。在此，我们研究STC1对成骨细胞生成过程中功能性异源二聚体复合物CALCRL/RAMP1的表达及活性的影响。与对照组相比，STC1在成骨细胞生成过程中未改变CALCRL和ramp1基因的表达。然而，在暴露于CGRP或STC1的7天前成骨细胞中，CALCRL/RAMP1的质膜空间分布发生了改变，并且两种肽均诱导了CALCRL和RAMP1的组装。CGRP可刺激7天成骨细胞和CALCRL/RAMP1转染的HEK293细胞中的cAMP积累，而STC1则无此作用。此外，STC1抑制了福司可林刺激的HEK293细胞中的cAMP积累，但对CALCRL/RAMP1转染的HEK293细胞无此作用。然而，STC1抑制了降钙素刺激的降钙素受体（CTR）HEK293转染细胞中的cAMP积累。总之，STC1通过抑制性G蛋白发出信号，在成骨细胞生成过程中调节CGRP受体的空间定位，并可能作为一种调节因子在骨形成过程中与降钙素肽成员相互作用。
