An optogenetic approach for regulating human parathyroid hormone secretion

Parathyroid hormone (PTH) plays a role in maintaining calcium and phosphorus homeostasis, and in secondary hyperparathyroidism excess PTH secretion contributes to bone loss. Here the authors report an optogenetic approach to inhibit PTH secretion in human hyperplastic parathyroid cells, and prevented hyperplastic parathyroid tissue-induced bone loss in mice. 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.

Automated summary

A new optogenetic approach was used to inhibit PTH secretion in human parathyroid cells and prevent bone loss in mice, providing a strategy to regulate PTH release and associated bone loss.