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    Home > Active Ingredient News > Endocrine System > Research progress of light regulation of parathyroid hormone secretion to interfere with bone loss

    Research progress of light regulation of parathyroid hormone secretion to interfere with bone loss

    • Last Update: 2022-03-08
    • Source: Internet
    • Author: User
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    Recently, Yang Fan's team from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and the Shenzhen-Hong Kong Brain Science Innovation Research Institute published research results entitled An optogenetic approach for regulating human parathyroid hormone secretion in Nature Communications
    .

    For 5 years, the research team innovatively applied optogenetic technology to the regulation of Parathyroid Hormone (PTH) secretion, through precise rhythmic regulation of PTH secretion, to interfere with bone loss caused by secondary hyperparathyroidism
    .

    This study expands the application of optogenetic technology in the field of bone and endocrine research, and provides a scientific basis for advancing the clinical translation of optogenetic technology
    .

    PTH is a hormone secreted by chief cells of the parathyroid gland and plays a crucial role in maintaining calcium and phosphorus homeostasis and bone metabolism
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    The secretion of PTH is regulated by the calcium sensing receptors (CaSR) on the chief cells of the parathyroid gland by sensing the blood calcium concentration
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    However, in hyperparathyroidism (hyperparathyroidism), the chief parathyroid cells cannot accurately sense changes in blood calcium concentration and feedback regulate the high level of PTH secretion, resulting in symptoms such as hypercalcemia, mood disorders, and bone loss.

    .

    The current treatments for secondary hyperparathyroidism, including parathyroidectomy and calcimimetic agents, cannot precisely and rhythmically regulate the secretion of PTH, so that the physiological regulation of PTH cannot be fully realized
    .

    The research team first found that the expression of CaSR in parathyroid cells of patients with secondary hyperparathyroidism decreased, the membrane potential and intracellular calcium response decreased in the face of extracellular calcium stimulation, and PTH was secreted at a high level
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    The use of optogenetic modulation of parathyroid cells can induce changes in membrane potential and intracellular calcium response, and inhibit PTH secretion
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    They further studied and found that light stimulation can inhibit the cAMP-PKA molecular pathway in parathyroid chief cells, while activating the phosphatase A2 (PLA2)-arachidonic acid (AA) signaling pathway, thereby effectively inhibiting the PTH of hyperparathyroid chief cells.
    synthesis and secretion
    .

    In order to further study the physiological significance of light-regulated PTH secretion, the research team established a secondary hyperparathyroidism rat model and a nude mouse model of human parathyroid tissue transplantation, and expressed the optogene in the animal's parathyroid gland in vivo.
    On the other hand, PTH secretion was effectively inhibited in vivo by light regulation
    .

    The researchers also developed a calcium-responsive automatic light regulation system, which can help parathyroid cells automatically respond to changes in extracellular calcium concentration, thereby achieving physiological regulation of PTH
    .

    More importantly, the inhibition of PTH secretion by rhythmic light can effectively regulate the process of bone remodeling, promote osteogenesis and inhibit bone resorption: the number of osteoblasts in the cancellous bone of mice increases, and the number of osteoclasts decreases; the density of cancellous bone increases , the number of trabecular bone increased
    .

    This indicates that optogenetic regulation of PTH can effectively interfere with bone metabolism and improve bone loss in hyperparathyroidism model animals
    .

    In this study, optogenetics was applied to the regulation of PTH secretion for the first time, and the precise rhythmic regulation of PTH was achieved; furthermore, the precise regulation of PTH rhythmic secretion was used to intervene in bone metabolism, laying a foundation for analyzing the neuroendocrine mechanism of bone loss caused by anxiety, and for effective Intervening the abnormal secretion of PTH and relieving the symptoms of anxiety and bone loss related to hyperparathyroidism provides a scientific basis
    .

    Relevant research work has been supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences, Guangdong Province and Shenzhen
    .

    Rhythmic light regulates parathyroid hormone secretion to interfere with bone loss Source: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
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