Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1

Hui Li, Dongmei Wang, Lisam Shanjukumar Singh, Michael Berk, Haiyan Tan, Zhenwen Zhao, Rosemary Steinmetz, Kashif Kirmani, Gang Wei, Yan Xu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK) activation and nitric oxide (NO) production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.

Original languageEnglish
Article numbere5705
JournalPLoS One
Volume4
Issue number5
DOIs
StatePublished - May 28 2009

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ovarian neoplasms
Macrophages
G-Protein-Coupled Receptors
Osteogenesis
Ovarian Neoplasms
carcinogenesis
Carcinogenesis
osteoclasts
Protons
mice
Bone
Osteoclasts
Cells
Thioglycolates
macrophages
Extracellular Signal-Regulated MAP Kinases
Tumor Suppressor Genes
protons
Lipopolysaccharides
Tumors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1. / Li, Hui; Wang, Dongmei; Singh, Lisam Shanjukumar; Berk, Michael; Tan, Haiyan; Zhao, Zhenwen; Steinmetz, Rosemary; Kirmani, Kashif; Wei, Gang; Xu, Yan.

In: PLoS One, Vol. 4, No. 5, e5705, 28.05.2009.

Research output: Contribution to journalArticle

Li, Hui ; Wang, Dongmei ; Singh, Lisam Shanjukumar ; Berk, Michael ; Tan, Haiyan ; Zhao, Zhenwen ; Steinmetz, Rosemary ; Kirmani, Kashif ; Wei, Gang ; Xu, Yan. / Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1. In: PLoS One. 2009 ; Vol. 4, No. 5.
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