The parathyroid gland is one of the secretory glands of the human body, the main function is to secrete parathyroid hormone (PTH), which regulates the metabolism of calcium and phosphorus in the body. Hyperparathyroidism (hyperparathyroidism) is a class of endocrine diseases caused by abnormal secretion of parathyroid hormone, which is mainly manifested clinically as hypercalcemia, emotional abnormalities, bone loss and other symptoms, and the effect of traditional treatment methods such as surgical resection and drug therapy is not perfect.
Nanfang + reporter learned that on February 9, the latest research results of the Yang Fan team of the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences (hereinafter referred to as the "Shenzhen Advanced Institute") and the Shenzhen-Hong Kong Brain Science Innovation Research Institute were published in Nature-Communications. The research team lasted for 5 years, innovatively applied optogenetic technology to the secretion regulation of parathyroid hormone, and independently developed a calcium-responsive automatic photomodulation system, which can achieve accurate rhythmic regulation of parathyroid hormone secretion, and then intervene in the symptoms of 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 promoting the clinical translation of optogenetic technology. Yang Fan, researcher of Shenzhen Advanced Institute, and Zhang Xinzhou, director of the Department of Nephrology of Shenzhen People's Hospital, are co-corresponding authors; Liu Yunhui, associate researcher of Shenzhen Advanced Institute, Zhang Lu, postdoctoral fellow, and Dr. Hu Nan of Shenzhen People's Hospital are co-first authors; Shenzhen Advanced Institute is the first unit.
Screenshot of the paper online.
PTH disorder? Regulate with "light"
According to the shenzhen advanced institute of scientific researchers, the secretion of parathyroid hormone has a rhythmic physiological law, when the human blood calcium concentration decreases, parathyroid hormone secretion will increase, respectively, acting on the bone, kidney and small intestine and other organs to promote calcium release and absorption, thereby upregulating the concentration of human blood calcium; and when the blood calcium concentration increases, the secretion of parathyroid hormone will decrease, thereby prompting blood calcium to fall back to normal levels.
During this physiological process, calcium-sensitive receptors on parathyroid cells act as "monitors" that can sense blood calcium concentrations to regulate the secretion of parathyroid hormone. However, this "monitor" does not work in patients with secondary hyperparathyroidism.
Yang Fan said: "Parathyroid hormone plays an important role in maintaining calcium and phosphorus balance and bone metabolism, in pathological conditions, due to the inability of calcium-sensitive receptors to accurately feel the change in blood calcium concentration, which in turn makes parathyroid hormone secretion abnormal, resulting in symptoms such as calcium and phosphorus metabolism disorders and bone loss in the body, there is no ideal way to achieve accurate rhythmic regulation of parathyroid hormone."
Rhythmic light-regulated parathyroid hormone secretion intervenes in bone loss. (Courtesy of the interviewed research team)
It is reported that the Yang Fan team of Shenzhen Advanced Institute has been committed to the research of neuromodulation of bone metabolism for many years, and the research team cooperated with Shenzhen People's Hospital to find in the samples of patients with secondary hyperparathyroidism that the use of optogenetic means can accurately regulate the secretion of parathyroid hormone.
"Optogenetic means is a light control technology, just like turning on the light switch, when we 'transport' the light-sensitive protein into the main cell of the parathyroid gland through the viral carrier, the molecular pathways within the cell can be activated in the form of light stimulation, effectively inhibiting the synthesis and secretion of parathyroid hormone, and achieving precise regulation of parathyroid hormone." Liu Yunhui said.
Achieve rhythmic regulation to improve bone loss
Zhang Xinzhou said: "In the clinical treatment of hyperparathyroidism, the main means at present include surgical removal of the parathyroid glands, or drug treatment of patients. Taking surgical resection as an example, after the hypertrophic parathyroid gland is removed, although it can reduce the secretion of parathyroid hormone, it cannot regulate the secretion of parathyroid hormone in a precise rhythm, so that its physiological regulation cannot be achieved, and the symptoms of hypercalcemia and bone loss in patients cannot be completely alleviated. ”
In order to study the physiological significance of light-regulated parathyroid hormone secretion, the researchers established a rat model of secondary hyperparathyroidism induced by a low-calcium and high-phosphorus diet and a nude mouse model of human parathyroid tissue transplantation. 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 hyperthyroidism can be effectively inhibited through light regulation.
The researchers further developed a calcium-responsive automatic photoregulation system that helps parathyroid cells automatically respond to changes in extracellular calcium concentrations, thereby achieving physiological regulation of parathyroid hormone.
"More importantly, we effectively regulated the bone remodeling process by rhythmically inhibiting parathyroid hormone secretion, promoting bone production and inhibiting bone resorption; we found that after using light to regulate parathyroid tissue, the number of osteoblasts in mouse cancellous bone increased and the number of osteoclasts decreased." Yang Fan said that the use of optogenetic technology to achieve the regulation of parathyroid hormone rhythm can effectively intervene in bone metabolism, improve bone loss in animal models of hyperparathyroidism, and provide new ideas and methods for clinical intervention in bone loss caused by abnormal increase in parathyroid hormone secretion.
For a long time, optogenetic means have been used to study and analyze brain neural circuits, and expanding the clinical application of optogenetic means is an important direction of concern in the industry. The research team innovatively used optogenetic technology to study and regulate the secretion of parathyroid hormone, which not only expanded the application field of optogenetic technology in the clinic, but also provided new ideas for the research and treatment of clinical diseases.
Yang Fan said that the research team will further work closely with the hospital to promote optogenetic technology to regulate the clinical transformation of parathyroid hormone and provide more practical help for the treatment of hyperparathyroidism and other related diseases.
[Reporter] Ma Fang
【Author】 Ma Fang
【Source】 Southern Press Media Group South + client