β-Arrestin 1 in Thyrotropin Receptor Signaling in Bone: Studies in Osteoblast-Like Cells.

Abstract

A direct action of thyrotropin (TSH, thyroid-stimulating hormone) on bone precursors in humans is controversial. Studies in rodent models have provided conflicting findings. We used cells derived from a moderately differentiated osteosarcoma stably overexpressing human TSH receptors (TSHRs) as a model of osteoblast precursors (U2OS-TSHR cells) to investigate TSHR-mediated effects in bone differentiation in human cells. We review our findings that (1) TSHR couples to several different G proteins to induce upregulation of genes associated with osteoblast activity-interleukin 11 (IL-11), osteopontin (OPN), and alkaline phosphatase (ALPL) and that the kinetics of the induction and the G protein-mediated signaling pathways involved were different for these genes; (2) TSH can stimulate β-arrestin-mediated signal transduction and that β-arrestin 1 in part mediates TSH-induced pre-osteoblast differentiation; and (3) TSHR/insulin-like growth factor 1 (IGF1) receptor (IGF1R) synergistically increased OPN secretion by TSH and IGF1 and that this crosstalk was mediated by physical association of these receptors in a signaling complex that uses β-arrestin 1 as a scaffold. These findings were complemented using a novel β-arrestin 1-biased agonist of TSHR. We conclude that TSHR can signal via several transduction pathways leading to differentiation of this model system of human pre-osteoblast cells and, therefore, that TSH can directly regulate these bone cells.

• Authors: Alisa Boutin, Marvin C Gershengorn, Susanne Neumann
• Journal: Frontiers in endocrinology (Front Endocrinol (Lausanne)) Vol. 11 Pg. 312 ( 2020) ISSN: 1664-2392 [Print] Switzerland
• PMID: 32508750 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Review)
• Copyright: Copyright © 2020 Boutin, Gershengorn and Neumann.

Chemical References

• Receptors, Thyrotropin
• beta-Arrestin 1

Topics

• Animals
• Bone and Bones (cytology, metabolism)
• Cell Differentiation
• Humans
• Osteoblasts (cytology, metabolism)
• Osteosarcoma (metabolism, pathology)
• Receptors, Thyrotropin (metabolism)
• Signal Transduction
• beta-Arrestin 1 (metabolism)