Light regulation of parathyroid hormone secretion in the intervention of bone loss has been advanced

2022-04-29 0 By

Recently,Prof. Fan Yang and his team from Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences published An Optogenetic Approach for Regulating human in Nature CommunicationsResearch results of Parathyroid hormone.In this study, we explored the role of photogenetic technology in the regulation of Parathyroid Hormone (PTH) secretion, which regulates PTH secretion rhythmically and interferes with bone loss induced by secondary hyperparathyroidism.This study expanded the application of photogenetic technology in bone and endocrine research, and provided scientific basis for promoting the clinical transformation of photogenetic technology.PTH is a hormone secreted by the main cells of parathyroid gland, which plays an important role in maintaining calcium and phosphorus homeostasis and bone metabolism.Regulation of PTH secretion is realized by Calcium sensitive receptors (CaSR) on the main cells of the parathyroid gland that sense blood Calcium concentration.However, in hyperparathyroidism (hyperparathyroidism), the main cells of the parathyroid gland are unable to accurately detect changes in blood calcium concentration and respond to high levels of PTH secretion, resulting in hypercalcemia, mood abnormalities, and bone loss.Current treatments for secondary hyperparathyroidism, including parathyroidectomy and calcium mimics, cannot accurately and rhythmically regulate PTH secretion, thus making the physiological regulation of PTH in the body unable to be fully realized.The team first found that in patients with secondary hyperparathyroidism, CaSR expression in parathyroidism cells decreased, membrane potential and intracellular calcium response decreased, and PTH secretion was high in response to extracellular calcium stimulation.Regulation of parathyroid cells by optogenetics induces changes in membrane potential and intracellular calcium response, and inhibits PTH secretion.We further found that photostimulation inhibited camp-PKA pathway and activated phosphoesterase A2 (PLA2) -arachidonic acid (AA) signaling pathway in parathyroid main cells, thus effectively inhibiting PTH synthesis and secretion in parathyroid main cells.In order to further study the physiological significance of photoregulation of PTH secretion, the research team established a rat model of secondary hyperparathyroidism and a nude mouse model of human parathyroid tissue transplantation, respectively. The photogene was expressed in vivo on parathyroid glands of animals, and PTH secretion was effectively inhibited by photoregulation in vivo.We have also developed a calcium-responsive photoregulatory system that can help parathyroid cells respond to changes in extracellular calcium concentration, thereby achieving physiological regulation of PTH.More importantly, rhythmic photoinhibition of PTH secretion can effectively regulate the process of bone remodeling, promote bone formation and inhibit bone resorption: the number of osteoblasts in cancellous bone of mice increased, while the number of osteoclasts decreased.The density of cancellous bone increased and the number of bone trabeculae increased.These results suggest that photogenetic regulation of PTH can effectively intervene in bone metabolism and improve bone loss in hyperparathyroidism model animals.In this study, optogenetics was applied to PTH secretion regulation for the first time, realizing the precise rhythm regulation of PTH.Further intervention of bone metabolism through precise regulation of PTH rhythm secretion laid a foundation for the analysis of the neuroendocrine mechanism of bone loss induced by anxiety, and provided a scientific basis for effective intervention of abnormal PTH secretion and relief of hyperparathyroidism related anxiety and bone loss symptoms.Related research work has been supported by the National Natural Science Foundation of China, The Chinese Academy of Sciences, Guangdong Province and Shenzhen Project.Rhythmic light regulates parathyroid hormone secretion and interferes with bone loss.Email address: jpbl@jp.jiupainews.com