An optogenetic approach for regulating human parathyroid hormone secretion

Yunhui Liu, Lu Zhang, Nan Hu, Jie Shao, Dazhi Yang, Changshun Ruan, Shishu Huang, Liping Wang, William W. Lu, Xinzhou Zhang () and Fan Yang ()
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Yunhui Liu: Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions
Lu Zhang: Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions
Nan Hu: The Second Clinical Medical College of Jinan University
Jie Shao: Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions
Dazhi Yang: Huazhong University of Science and Technology
Changshun Ruan: Chinese Academy of Sciences (CAS)
Shishu Huang: West China Hospital of Sichuan University
Liping Wang: Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions
William W. Lu: The University of Hong Kong
Xinzhou Zhang: The Second Clinical Medical College of Jinan University
Fan Yang: Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors (CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.

Date: 2022
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DOI: 10.1038/s41467-022-28472-9

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