Abstract
The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling.
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Acknowledgements
We gratefully acknowledge the late John Martin (Harvard School of Dental Medicine μCT Core Facility) for his expertise and participation in this study. Histological preparation and staining was performed by Dr. Keith Condon (Indiana University School of Medicine).
Funding
This study was supported by a Marian University College of Osteopathic Medicine Faculty Research Development Award issued to JWL, Iowa Osteopathic Education and Research funds issued to EMW, and other intramural funds.
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JWL, BJD, and LP conceived of, designed, and supervised the study. MSE, NW, JBN, MP, HEF, JWA, SRS, AB, RS, EMW, JN, and HD generated the data and performed the statistical analyses. All authors interpreted the results, and JWL, BJD, NW, and TDW drafted the manuscript. All authors read and approved the final manuscript.
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Eaton, M.S., Weinstein, N., Newby, J.B. et al. Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption. J Physiol Biochem 74, 3–8 (2018). https://doi.org/10.1007/s13105-017-0596-7
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DOI: https://doi.org/10.1007/s13105-017-0596-7