Nature Communications｜Light regulates parathyroid hormone secretion to interfere with bone loss

Using "light" to regulate parathyroid hormone to improve bone loss The parathyroid gland is one of the secretory glands of the human body.
Its main function is to secrete parathyroid hormone (PTH) and regulate the metabolism of calcium and phosphorus in the body
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Hyperparathyroidism (Hyperparathyroidism) is a type of endocrine disease caused by abnormal secretion of parathyroid hormone
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Traditional treatment methods such as surgical resection and drug therapy are not perfect, and there are even risks such as postoperative neoplasia
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On February 9, the latest research results of Yang Fan's team from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and Shenzhen-Hong Kong Brain Science Innovation Institute were published in Nature-Communications
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The research team has spent 5 years innovatively applying optogenetic technology to the regulation of parathyroid hormone secretion, and independently developed a calcium-responsive automatic light regulation system, which can achieve precise rhythmic regulation of parathyroid hormone secretion, and then intervene.
Bone loss symptoms due to secondary hyperparathyroidism
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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
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Researcher Yang Fan of Shenzhen Advanced Institute and Director Zhang Xinzhou of the Department of Nephrology of Shenzhen People's Hospital are the co-corresponding authors; Associate Researcher Liu Yunhui, Postdoctoral Zhang Lu of Shenzhen Advanced Institute and Dr.
Hu Nan of Shenzhen People's Hospital are the co-first authors; Shenzhen Advanced Institute is the first unit
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PTH disorders? Using "light" to regulate the secretion of parathyroid hormone has a rhythmic physiological law.
When the blood calcium concentration of the human body decreases, the secretion of parathyroid hormone will increase, and it will act on the bones, kidneys and small intestines and other organs to promote calcium release and absorption.
, so as to increase the concentration of human blood calcium; and when the concentration of blood calcium increases, the secretion of parathyroid hormone will decrease, thus prompting the blood calcium to fall back to the normal level
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In this physiological process, the calcium-sensing receptors on parathyroid cells play the role of "monitors", which can sense the blood calcium concentration to realize the regulation of the secretion of parathyroid hormone
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However, this "monitor" does not work in patients with secondary hyperparathyroidism
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"Parathyroid hormone plays an important role in maintaining calcium and phosphorus balance and bone metabolism; in pathological conditions, because calcium-sensitive receptors cannot accurately sense changes in blood calcium concentration, parathyroid hormone secretion is abnormal, resulting in calcium and phosphorus metabolism in the body.
Disorders and bone loss and other symptoms, there is currently no ideal method to achieve precise rhythmic regulation of parathyroid hormone
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" Yang Fan said
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For a long time, the team of Yang Fan from Shenzhen Advanced Institute has been devoted to the research of neural regulation of bone metabolism.
The research team cooperated with Shenzhen People's Hospital and found in samples from patients with secondary hyperparathyroidism that the use of optogenetics can accurately Regulates the secretion of parathyroid hormone
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 "Optogenetic means is a light-controlled technology, just like turning on the light switch, when we 'transport' the light-sensitive protein into the parathyroid chief cell through the viral vector, the light-stimulation method can activate the intracellular Molecular pathway, effectively inhibit the synthesis and secretion of parathyroid hormone, and achieve precise regulation of parathyroid hormone
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" Liu Yunhui said
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Optogenetic stimulation can induce changes in the membrane potential of parathyroid cells and intracellular calcium response to achieve rhythmic regulation and improve bone loss.
"In the clinical treatment of hyperparathyroidism, the current treatment methods for hyperparathyroidism mainly include parathyroid surgery.
excision, or administering medication to the patient
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Taking surgical resection as an example, after the hyperplasia of the parathyroid gland is removed, although the secretion of parathyroid hormone can be reduced, it cannot precisely rhythmically regulate the secretion of parathyroid hormone, making its physiological regulation impossible, and the patient's high blood pressure.
Symptoms of calcemia and bone loss are also not completely relieved
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Zhang Xinzhou said
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In order to study the physiological significance of light regulation of parathyroid hormone secretion, the researchers established a low-calcium and high-phosphorus diet-induced secondary hyperparathyroidism rat model and a nude mouse model of human parathyroid tissue transplantation.

The
experimental results show that light-sensitive proteins can be expressed on the parathyroid glands of animals, and the secretion of parathyroid hormone in animal models of hyperparathyroidism can be effectively inhibited by light regulation
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The researchers further developed a calcium-responsive automatic light regulation system, which The system can help parathyroid cells to automatically respond to changes in extracellular calcium concentration, thereby achieving physiological regulation of parathyroid hormone
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"More importantly, by rhythmically inhibiting parathyroid hormone secretion, we effectively regulate the The process of bone remodeling promotes bone formation and inhibits bone resorption; we found that after regulating parathyroid tissue with light, the number of osteoblasts in the cancellous bone of mice increased and the number of osteoclasts decreased
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Yang Fan said that the use of optogenetic technology to realize the rhythmic regulation of parathyroid hormone can effectively interfere with bone metabolism, improve bone loss in animal models of hyperparathyroidism, and provide new opportunities for clinical intervention in bone loss caused by abnormally increased parathyroid hormone secretion.
Ideas and new methods
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Rhythmic light regulation of parathyroid hormone secretion to interfere with bone loss Optogenetic methods have been used to study and analyze brain neural circuits.
Expanding the clinical application of optogenetic methods is an important direction in the industry
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The sub-research team innovatively used optogenetic technology to study the regulation of parathyroid hormone secretion, which not only expanded the application field of optogenetic technology in clinical practice, but also provided new ideas for the research and treatment of clinical diseases
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Yang Fan said that the research team will further work closely with the hospital to promote the clinical translation of optogenetic technology to regulate parathyroid hormone, and provide more practical help for the treatment of hyperparathyroidism and other related diseases
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Paper link: https://