ABSTRACT
Osteocalcin (OCN) regulates the physiological structure and function of various peripheral tissues and organs, and plays a central regulatory role, which is tightly associated with higher-level cognitive functions such as learning and memory. Studies have shown that OCN can enter the central nervous system through the blood-brain barrier and bind to GPR158 and GPR37, members of the G protein-coupled receptor (GPCR) family on the membrane of neurons or glial cells, activate or inhibit relevant intracellular signalling pathways, and then change the physiological activities of neurons or glial cells. In the brain, the role of OCN mainly includes regulating the synthesis and release of neurotransmitters such as serotonin, dopamine, norepinephrine and γ-aminobutyric acid, increasing the expression of brain-derived neurotrophic factor, promoting hippocampal neurogenesis, enhancing hippocampal neuron autophagy and maintaining myelin homeostasis, among others. Furthermore, OCN can also be involved in the regulation of the pathophysiological process of multiple neurodegenerative diseases. In Alzheimer's disease (AD), OCN treatment reduces β-amyloid protein (Aβ) deposition and Aβ-induced cytotoxicity in part, thereby improving learning and memory deficits; in Parkinson's disease (PD), OCN treatment inhibits the loss of substantia nigra and striatum dopaminergic neurons, increases the content of tyrosine hydroxylase and decreases neuroinflammation, thereby alleviating motor dysfunction. By analyzing the structure and function of GPR158 and GPR37, analyzing the role of OCN in the brain and its biological mechanism, and exploring the effect of OCN on neurodegenerative diseases such as AD and PD, this paper aims to provide a basis for further screening new targets to promote brain health.
ABSTRACT
Objective To observe the effect of silencing the expression of ADM using RNA interfering technique on the expression ofβ-catenin and terminal differentiation of osteosarcoma cells.Methods After the intervention of 0 h,48 h and 72 h by ADM siRNA,we observed the change of distribution ofβ-catenin in F5M2 using immunocytochemistry staining.The expression levels of total and phosphorylatedβ-catenin and GSK3βwere detected by Western blot after the intervention by ADM siRNA.The F5 M2 cells treated with ADM siRNA were subjected to HE staining,alkaline phosphatase (ALP)assay and immunocytochemistry staining to investigate the biological effects of ADM siRNA on the morphology and terminal differentiation of F5M2 cells.Results After the intervention of 0 h,48 h and 72 h by ADM siRNA,the distribution ofβ-catenin was transferred from the cytoplasm to the nucleus.ADM siRNA downregulated the expression level of P-β-catenin and upregulated P-GSK3βdetected by Western blot.HE staining revealed that the configuration of F5M2 had undergone restorational changes similar to those of normal cells after ADM siRNA treatment.ALP assay and immunocytochemistry staining showed that the expression of the earlier and later molecular biomarkers of terminal differentiation,including ALP and osteocalcin were strongly positive.Conclusion Silencing the expression of ADM can activateβ-catenin to transfer to the nucleus from the cytoplasm,and induce osteosarcoma cells to make terminal differentiation through activatingβ-catenin signaling pathway.