NPY and CGRP Inhibitor Influence on ERK Pathway and Macrophage Aggregation during Fracture Healing

Tang, Peng; Duan, Chunguang; Wang, Zheng; Wang, Chunmei; Meng, Guolin; Lin, Kaifeng; Yang, Qian; Yuan, Zhi

doi:10.1159/000468405

Cited by 27 publications

(32 citation statements)

References 22 publications

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“…It has been demonstrated that NPY could accelerate osteoblastic differentiation of MSCs and fracture healing, and the level of NPY was increased during the early fracture healing [14,19]. In this study, our results suggest that MLT promoted cell proliferation and migration by NPY and NPY1R in MSCs.…”

Section: Discussionsupporting

confidence: 62%

Melatonin Induces Osteoblastic Differentiation of Mesenchymal Stem Cells and Promotes Fracture Healing in a Rat Model of Femoral Fracture via Neuropeptide Y/Neuropeptide Y Receptor Y1 Signaling

Dong

Zhu

et al. 2018

Pharmacology

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The function of melatonin (MLT) in promoting fracture healing has been demonstrated in previous studies. However, the molecular mechanism underlying therapeutic effects of MLT is not entirely clear. In this study, mesenchymal stem cells (MSCs) were isolated from rat bone marrow and identified by flow cytometry. We found that MLT treatment upregulated the neuropeptide Y (NPY) and NPY receptor Y1 (NPY1R) expression, and promoted the proliferation and migration of MSCs, which was suppressed by BIBP3226, an inhibitor of NPY1R. Moreover, the levels of NPY and NPY1R in MSCs undergoing osteoblastic differentiation were upregulated after MLT administration. MLT-induced osteoblastic differentiation of MSCs was suppressed by BIBP3226 treatment, as evidenced by decreased levels of alkaline phosphatase (ALP), collagen type I α1 chain, osteocalcin, and runt-related transcription factor 2, downregulated activity of ALP, as well as reduced calcium nodule formation. Furthermore, we demonstrated that MLT could promote fracture healing in a rat model of femoral fracture, which was accompanied by the elevated expression of NPY and NPY1R. The administration of BIBP3226 inhibited fracture healing mediated by MLT. To sum up, our results show that MLT promotes osteoblastic differentiation of MSCs and fracture healing by NPY/NPY1R signaling.

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Section: Discussionsupporting

confidence: 62%

Melatonin Induces Osteoblastic Differentiation of Mesenchymal Stem Cells and Promotes Fracture Healing in a Rat Model of Femoral Fracture via Neuropeptide Y/Neuropeptide Y Receptor Y1 Signaling

Dong

Zhu

et al. 2018

Pharmacology

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“…Different Y receptors mediate different processes and diseases such as food intake [17], obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, fracture healing [18] and many cancers [19-26]. By binding to different receptors，NPY plays various roles in human biological processes, and sometimes can even function quite differently.…”

Section: Introductionmentioning

confidence: 99%

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

et al. 2017

Cell Physiol Biochem

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Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

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“…The mononuclear phagocyte system plays an important role in the immune system [24,25], and macrophages have different names in different organs, for example, Kupffer cells in the liver, Langerhans cells in the lung, microglia in the central nervous system, and osteoclasts in bone [26]. Given that many organs have been shown to produce PCT during sepsis and surgery, it is essential to conduct further studies on the contribution made by the mononuclear phagocyte system and the degree of PCT expression.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Macrophages are the Cell Source of Hepatic Procalcitonin in Acute Liver Failure

Zheng¹,

Ye²,

Xue³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Serum procalcitonin (PCT) is elevated in acute liver failure (ALF), but the expression of PCT in the liver has not been elucidated. We aimed to clarify the regulation of hepatic PCT expression and the cell sources in ALF. Methods: Human monocytic leukemia line U937 cells were treated with 12-O-tetradecanoylphorbol-l3-acetate (PMA) (100 ng/ mL) for 24 h to induce activated macrophages. In the presence of lipopolysaccharide (LPS, 1 μg/mL), activated macrophages and human hepatocyte line L02 cells were incubated with LPS or co-cultured for 0, 2, 6, and 24 h. In an in vivo experiment, male C57BL/6 mice were challenged with intraperitoneal LPS/D-galactosamine (LPS/D-GalN). Serum liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic chemical analyzer. Inflammatory mediators were measured by real-time PCR and liver histology was examined by hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). Results: LPS induced the upregulation of PCT mRNA in U937-activated macrophages but not in L02 cells. When co-cultured with L02 cells, the expression of PCT mRNA of activated macrophages was upregulated compared to controls; however, the activated macrophages did not induce the expression of PCT mRNA in L02 cells in the presence of LPS. Moreover, serum liver enzymes (ALT, AST), inflammation, necrosis, and hepatic expression of PCT were significantly elevated in the LPS/D-GalN-challenged ALF mouse model. IHC revealed that PCT expression was co-localized with hepatic macrophages. Conclusions: Hepatic PCT expression is upregulated in ALF. Hepatic macrophages but not hepatocytes are the cell source of hepatic PCT expression.

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NPY and CGRP Inhibitor Influence on ERK Pathway and Macrophage Aggregation during Fracture Healing

Cited by 27 publications

References 22 publications

Melatonin Induces Osteoblastic Differentiation of Mesenchymal Stem Cells and Promotes Fracture Healing in a Rat Model of Femoral Fracture via Neuropeptide Y/Neuropeptide Y Receptor Y1 Signaling

Melatonin Induces Osteoblastic Differentiation of Mesenchymal Stem Cells and Promotes Fracture Healing in a Rat Model of Femoral Fracture via Neuropeptide Y/Neuropeptide Y Receptor Y1 Signaling

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

Hepatic Macrophages are the Cell Source of Hepatic Procalcitonin in Acute Liver Failure

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