Chemogenetic modulation of parathyroid hormone secretion alleviates osteoporosis in ovariectomized rats.

Parathyroid hormone (PTH) is critical for regulating calcium and phosphate homeostasis, and its dysregulation contributes to osteoporosis. Current methods for precise control of PTH secretion are limited. This study explores chemogenetic tools to regulate PTH secretion in parathyroid chief cells via Gq/Gi signaling. In vitro, we found that activation of hM3Dq-expressing cells increased PTH release, while hM4Di inhibited it. In vivo, hM3Dq activation improved bone structure and reduced bone loss in an ovariectomized rat model. These findings suggest chemogenetics as a promising approach for modulating PTH and offering potential therapeutic strategies for bone health and related disorders.