It took five years to successfully control parathyroid hormone with "light"

When it comes to the treatment of endocrine diseases such as hyperthyroidism and hyperparathyroidism, people will think of drugs and surgery.
Who would have thought that "light" can also be used? 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
.

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.
Symptoms of bone loss (bone loss, decreased bone density, etc.
) caused by secondary hyperparathyroidism (click "read the original text" at the end of the article to see the paper)
.

PTH disorders? Using "light" to regulate 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
.

Hyperparathyroidism (Hyperparathyroidism) is a type of endocrine disease caused by abnormal secretion of parathyroid hormone
.

Traditional treatment methods such as surgical resection and drug therapy are not perfect, and there are even risks such as postoperative neoplasia
.

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, small intestine and other organs to promote the release and absorption of calcium, thereby up-regulating human blood.
When the concentration of calcium in the blood increases, the secretion of parathyroid hormone will decrease, which will cause the blood calcium to fall back to the normal level
.

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
.

However, this "monitor" does not work in patients with secondary hyperparathyroidism
.

Parathyroid hormone plays an important role in maintaining calcium and phosphorus balance and bone metabolism; in pathological conditions, calcium-sensing receptors cannot accurately sense changes in blood calcium concentration, resulting in abnormal secretion of parathyroid hormone, resulting in calcium and phosphorus metabolism disorders in the body There is no ideal method to achieve precise rhythmic regulation of parathyroid hormone
.

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
.

Optogenetic means is a light-controlled technology, just like turning on a light switch.
When researchers "transport" light-sensitive proteins into parathyroid chief cells through viral vectors, they can activate intracellular light-stimulation by means of light stimulation.
Molecular pathway, effectively inhibit the synthesis and secretion of parathyroid hormone, and achieve precise regulation of parathyroid hormone
.

Realizing rhythmic regulation and improving bone loss In the clinical treatment of hyperparathyroidism, the current treatment methods for hyperparathyroidism mainly include surgical resection of the parathyroid gland, or drug therapy for patients
.

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
.

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 the light-sensitive protein can be expressed in the parathyroid glands of animals, and the secretion of parathyroid hormone in an animal model of hyperparathyroidism can be effectively inhibited by light regulation
.

The researchers further 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 parathyroid hormone
.

The researchers found that by rhythmically inhibiting the secretion of parathyroid hormone, it effectively regulates the process of bone remodeling, promotes bone formation and inhibits bone resorption.
After using light to regulate parathyroid tissue, the osteoblasts of mouse cancellous bone The number increased and the number of osteoclasts decreased
.

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 ideas and methods for clinical intervention in bone loss caused by abnormally increased parathyroid hormone secretion.

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Figure 2.
Rhythmic light regulates parathyroid hormone secretion to intervene in bone loss.
Conclusion Optogenetics has always been used to study and analyze brain neural circuits.
Expanding the clinical application of optogenetics is an important direction in the industry
.

The 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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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 of the paper; 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 author unit
.

The research team will further cooperate 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
.