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Responsible editorIn recent years, research by Enzyme Beauty has found that bones are also an endocrine organ in addition to supporting and protecting organs
.
Through the secretion of various bone-derived factors, bones can act on various organs other than bones, including the central nervous system, through the secretion of various bone-derived factors, and participate in the regulation of body homeostasis.
The development of the brain has important regulatory functions
.
However, the specific mechanisms by which bone-derived factors regulate extra-osseous organs, especially the functions of the central nervous system, are not yet fully understood.
To clarify the relevant mechanisms is useful for finding therapeutic targets for maintaining normal nervous system function and related diseases from the perspective of regulating bone homeostasis.
Points, and new ways to maintain the body’s health are of great significance
.
Osteocalcin (OCN) is a functional bone-derived factor secreted by bones
.
A large number of studies have shown that OCN can act on peripheral tissues and organs such as the pancreas, reproductive system and muscles, and has important regulatory functions on the body's energy metabolism, reproduction and exercise capacity
.
It has been confirmed that the peripheral function of OCN is mediated by the G protein-coupled receptor GPRC6A
.
Recent studies have found that OCN can also cross the blood brain barrier (Blood Brain Barrier, BBB) to affect the central nervous system, affecting brain development and central nervous system Body [5]
.
However, the regulatory function of the bone-derived factor OCN on the central nervous system is still poorly understood, and there may be other new central receptors for OCN
.
On October 22, 2021, a research team led by Researcher Li Xiang from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, published a research paper titled Osteocalcin attenuates oligodendrocyte differentiation and myelination via GPR37 signaling in the mouse brain in Science Advances , Discovered for the first time that osteocalcin has a key regulatory effect on the differentiation and myelination of oligodendrocytes in the central nervous system; discovered and identified a new receptor that mediates osteocalcin, a new central function: G protein Coupled receptor GPR37
.
First, the study was carried out using OCN knockout mice.
Based on immunostaining, it was found that after OCN knockout, the expression of myelin-related marker genes in the white matter region of the mouse central system increased, and then protein hybridization was used to verify; and the OCN gene was found by electron microscopy analysis The thickness of myelin sheath increased after knockout, further confirming that OCN has a regulatory effect on oligodendrocytes
.
Next, in order to explore whether OCN affects oligodendrocytes through the regulation of cell proliferation or cell differentiation, primary oligodendrocyte culture and OCN gene knockout animals were used to analyze the effects of OCN on oligodendrocyte proliferation.
The results show that: OCN has little effect on the proliferation of oligodendrocyte precursor cells, but inhibits its differentiation function
.
Furthermore, the author analyzed the difference in RNA expression in the corpus callosum region of OCN gene knockout mice and wild mice by RNA sequencing, and found and determined that GPR37 may be the central receptor of OCN; and then used an in vitro expression system based on HEK293 cells to combine a variety of The intracellular signal detection system confirmed that OCN can activate intracellular signal transduction through GPR37; since GPR37 is highly expressed in oligodendrocytes, methods such as shRNA knockdown and GPR37 antibody inhibition confirmed that GPR37 can mediate OCN to oligodendrocytes.
Regulation of glial cell differentiation
.
Finally, the authors used GPR37 knockout mice and wild-type mice to further discover the effect of OCN in inhibiting the myelination of oligodendrocytes in mice in vivo; and use electron microscopy analysis to verify the central system myelination after GPR37 gene knockout The result of increased sheathing
.
Behavioral analysis (including hot plate and pupil light reflection) found that OCN and GPR37 gene knockout mice had abnormal conduction
.
The above results indicate that OCN regulates the differentiation and myelination of oligodendrocytes in the central nervous system through GPR37, which will provide an experimental basis for OCN as a potential peripheral target for the treatment of central myelinopathy
.
In this study, the use of knockout mice and primary cell culture analysis found that OCN has an important regulatory effect on the differentiation and myelination of oligodendrocytes in the central nervous system, and discovered and preliminarily identified the functions of OCN in the central nervous system.
The new receptor in regulation is GPR37
.
Oligodendrocytes are the key cells that form the myelin sheath of the central nervous system
.
They play a very critical role in maintaining the normal function of neurons, forming an insulating myelin structure, and assisting in the skipping and efficient transmission of bioelectrical signals .
The dysfunction of oligodendrocytes may damage the myelin structure, cause myelinopathy and neuronal damage, and lead to nervous system dysfunction, leading to a series of nervous system or mental diseases, such as multiple sclerosis.
sclerosis, MS)
.
Therefore, in-depth exploration of the new functions of OCN in oligodendrocytes and its internal mechanism, starting from the search for "peripheral-central" key regulatory molecules, to find new ways to maintain nervous system functions from the perspective of regulating bone function and bone-derived factors The measures provide a theoretical basis and provide a scientific basis for new strategies and new targets for clinical intervention of related neurological diseases
.
The first author of this article is the assistant researcher Dr.
Zhengjiang Qian, and the only corresponding author is Dr.
Xiang Li
.
This research is mainly based on the Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, and was completed in collaboration with the team of Researcher Wang Liping, Researcher Lu Zhonghua and Professor Chen Ying of Xiamen University
.
Original link: https:// Platemaker: 11 References 1.
NK Lee et al.
, Endocrine regulation of energy metabolism by the skeleton.
Cell 130, 456-469 (2007).
2.
F.
Oury et al.
, Endocrine Regulation of Male Fertility by the Skeleton.
Cell 144, 796-809 (2011) 3.
P.
Mera et al.
, Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise.
Cell Metab 23, 1078-1092 (2016).
4.
F.
Oury et al.
, Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions.
Cell 155, 228-241 (2013).
5.
L .
Khrimian et al.
, Gpr158 mediates osteocalcin's regulation of cognition.
Journal of Experimental Medicine 214, 2859-2873 (2017).
Reprinting instructions [Non-original articles] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
, The author has all legal rights, and offenders must be investigated
.
.
Through the secretion of various bone-derived factors, bones can act on various organs other than bones, including the central nervous system, through the secretion of various bone-derived factors, and participate in the regulation of body homeostasis.
The development of the brain has important regulatory functions
.
However, the specific mechanisms by which bone-derived factors regulate extra-osseous organs, especially the functions of the central nervous system, are not yet fully understood.
To clarify the relevant mechanisms is useful for finding therapeutic targets for maintaining normal nervous system function and related diseases from the perspective of regulating bone homeostasis.
Points, and new ways to maintain the body’s health are of great significance
.
Osteocalcin (OCN) is a functional bone-derived factor secreted by bones
.
A large number of studies have shown that OCN can act on peripheral tissues and organs such as the pancreas, reproductive system and muscles, and has important regulatory functions on the body's energy metabolism, reproduction and exercise capacity
.
It has been confirmed that the peripheral function of OCN is mediated by the G protein-coupled receptor GPRC6A
.
Recent studies have found that OCN can also cross the blood brain barrier (Blood Brain Barrier, BBB) to affect the central nervous system, affecting brain development and central nervous system Body [5]
.
However, the regulatory function of the bone-derived factor OCN on the central nervous system is still poorly understood, and there may be other new central receptors for OCN
.
On October 22, 2021, a research team led by Researcher Li Xiang from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, published a research paper titled Osteocalcin attenuates oligodendrocyte differentiation and myelination via GPR37 signaling in the mouse brain in Science Advances , Discovered for the first time that osteocalcin has a key regulatory effect on the differentiation and myelination of oligodendrocytes in the central nervous system; discovered and identified a new receptor that mediates osteocalcin, a new central function: G protein Coupled receptor GPR37
.
First, the study was carried out using OCN knockout mice.
Based on immunostaining, it was found that after OCN knockout, the expression of myelin-related marker genes in the white matter region of the mouse central system increased, and then protein hybridization was used to verify; and the OCN gene was found by electron microscopy analysis The thickness of myelin sheath increased after knockout, further confirming that OCN has a regulatory effect on oligodendrocytes
.
Next, in order to explore whether OCN affects oligodendrocytes through the regulation of cell proliferation or cell differentiation, primary oligodendrocyte culture and OCN gene knockout animals were used to analyze the effects of OCN on oligodendrocyte proliferation.
The results show that: OCN has little effect on the proliferation of oligodendrocyte precursor cells, but inhibits its differentiation function
.
Furthermore, the author analyzed the difference in RNA expression in the corpus callosum region of OCN gene knockout mice and wild mice by RNA sequencing, and found and determined that GPR37 may be the central receptor of OCN; and then used an in vitro expression system based on HEK293 cells to combine a variety of The intracellular signal detection system confirmed that OCN can activate intracellular signal transduction through GPR37; since GPR37 is highly expressed in oligodendrocytes, methods such as shRNA knockdown and GPR37 antibody inhibition confirmed that GPR37 can mediate OCN to oligodendrocytes.
Regulation of glial cell differentiation
.
Finally, the authors used GPR37 knockout mice and wild-type mice to further discover the effect of OCN in inhibiting the myelination of oligodendrocytes in mice in vivo; and use electron microscopy analysis to verify the central system myelination after GPR37 gene knockout The result of increased sheathing
.
Behavioral analysis (including hot plate and pupil light reflection) found that OCN and GPR37 gene knockout mice had abnormal conduction
.
The above results indicate that OCN regulates the differentiation and myelination of oligodendrocytes in the central nervous system through GPR37, which will provide an experimental basis for OCN as a potential peripheral target for the treatment of central myelinopathy
.
In this study, the use of knockout mice and primary cell culture analysis found that OCN has an important regulatory effect on the differentiation and myelination of oligodendrocytes in the central nervous system, and discovered and preliminarily identified the functions of OCN in the central nervous system.
The new receptor in regulation is GPR37
.
Oligodendrocytes are the key cells that form the myelin sheath of the central nervous system
.
They play a very critical role in maintaining the normal function of neurons, forming an insulating myelin structure, and assisting in the skipping and efficient transmission of bioelectrical signals .
The dysfunction of oligodendrocytes may damage the myelin structure, cause myelinopathy and neuronal damage, and lead to nervous system dysfunction, leading to a series of nervous system or mental diseases, such as multiple sclerosis.
sclerosis, MS)
.
Therefore, in-depth exploration of the new functions of OCN in oligodendrocytes and its internal mechanism, starting from the search for "peripheral-central" key regulatory molecules, to find new ways to maintain nervous system functions from the perspective of regulating bone function and bone-derived factors The measures provide a theoretical basis and provide a scientific basis for new strategies and new targets for clinical intervention of related neurological diseases
.
The first author of this article is the assistant researcher Dr.
Zhengjiang Qian, and the only corresponding author is Dr.
Xiang Li
.
This research is mainly based on the Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, and was completed in collaboration with the team of Researcher Wang Liping, Researcher Lu Zhonghua and Professor Chen Ying of Xiamen University
.
Original link: https:// Platemaker: 11 References 1.
NK Lee et al.
, Endocrine regulation of energy metabolism by the skeleton.
Cell 130, 456-469 (2007).
2.
F.
Oury et al.
, Endocrine Regulation of Male Fertility by the Skeleton.
Cell 144, 796-809 (2011) 3.
P.
Mera et al.
, Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise.
Cell Metab 23, 1078-1092 (2016).
4.
F.
Oury et al.
, Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions.
Cell 155, 228-241 (2013).
5.
L .
Khrimian et al.
, Gpr158 mediates osteocalcin's regulation of cognition.
Journal of Experimental Medicine 214, 2859-2873 (2017).
Reprinting instructions [Non-original articles] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
, The author has all legal rights, and offenders must be investigated
.
