Unknown

Dataset Information

0

Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation.


ABSTRACT: Although thyroid hormone (TH) is known to exert important effects on the skeleton, the nuclear factors constituting the TH receptor coactivator complex and the molecular pathways by which TH mediates its effects on target gene expression in osteoblasts remain poorly understood. A recent study demonstrated that the actions of TH on myoblast differentiation are dependent on diabetes- and obesity-related protein (DOR). However, the role of DOR in osteoblast differentiation is unknown. We found DOR expression increased during in vitro differentiation of bone marrow stromal cells into osteoblasts and also in MC3T3-E1 cells treated with TH. However, DOR expression decreased during cellular proliferation. To determine whether DOR acts as a modulator of TH action during osteoblast differentiation, we examined whether overexpression or knockdown of DOR in MC3T3-E1 cells affects the ability of TH to induce osteoblast differentiation by evaluating alkaline phosphatase (ALP) activity. ALP activity was markedly increased in DOR-overexpressing cells treated with TH. In contrast, loss of DOR dramatically reduced TH stimulation of ALP activity in MC3T3-E1 cells and primary calvaria osteoblasts transduced with lentiviral DOR shRNA. Consistent with reduced ALP activity, mRNA levels of osteocalcin, ALP, and Runx2 were decreased significantly in DOR shRNA cells. In addition, a common single nucleotide polymorphism (SNP), DOR1 found on the promoter of human DOR gene, was associated with circulating osteocalcin levels in nondiabetic subjects. Based on these data, we conclude that DOR plays an important role in TH-mediated osteoblast differentiation, and a DOR SNP associates with plasma osteocalcin in men.

SUBMITTER: Linares GR 

PROVIDER: S-EPMC3129842 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation.

Linares Gabriel R GR   Xing Weirong W   Burghardt Hans H   Baumgartner Bernhard B   Chen Shin-Tai ST   Ricart Wifredo W   Fernández-Real José Manuel JM   Zorzano Antonio A   Mohan Subburaman S  

American journal of physiology. Endocrinology and metabolism 20110405 1


Although thyroid hormone (TH) is known to exert important effects on the skeleton, the nuclear factors constituting the TH receptor coactivator complex and the molecular pathways by which TH mediates its effects on target gene expression in osteoblasts remain poorly understood. A recent study demonstrated that the actions of TH on myoblast differentiation are dependent on diabetes- and obesity-related protein (DOR). However, the role of DOR in osteoblast differentiation is unknown. We found DOR  ...[more]

Similar Datasets

| S-EPMC5770417 | biostudies-literature
| S-EPMC4038448 | biostudies-literature
| S-EPMC3571113 | biostudies-literature
| S-EPMC7823158 | biostudies-literature
| S-EPMC3234731 | biostudies-literature
2014-12-02 | GSE63724 | GEO
| S-EPMC2582919 | biostudies-literature
| S-EPMC4396470 | biostudies-literature
| S-EPMC8187789 | biostudies-literature
| S-EPMC2708864 | biostudies-literature