αCGRP Regulates Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Through ERK1/2 and p38 MAPK Signaling Pathways. 2022

Yixuan Jiang, and Na Xin, and Yi Xiong, and Yanjun Guo, and Ying Yuan, and Qin Zhang, and Ping Gong
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

As a typical neuropeptide richly distributed in central and peripheral nervous systems, α-calcitonin-gene-related peptide (αCGRP) has recently been found to play a crucial role in bone development and metabolism, but the mechanisms involved are not fully uncovered. Here, this study aimed to investigate the effects and underlying molecular mechanisms of αCGRP in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Using microarray technology, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses revealed that osteogenic properties of BMSCs were facilitated and mitogen-activated protein kinase (MAPK) signaling pathway was upregulated by αCGRP in this process. Through western blot assay, we proved that αCGRP led to an increased phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 MAPK signaling cascades in a time-dependent manner. And αCGRP could promote differentiative capacity of BMSCs, showing upregulated mRNA and protein expression level of alkaline phosphatase (Alp), collagen type 1 (Col-1), osteopontin (Opn), and runt-related transcription factor 2 (Runx2), as well as increased ALP activity and calcified nodules. The addition of ERK1/2 or p38 MAPK inhibitor-U0126 or SB203580, resulted in an impaired osteogenic differentiation of BMSCs. Besides, inactivation of this signal transduction had negative impacts on proliferative activity and apoptotic process of αCGRP-mediated BMSCs. Our findings demonstrated that MAPK signaling pathway, at least in part, was responsible for the enhanced BMSCs' osteogenesis induced by αCGRP, which might offer us promising strategies for bone-related disorders.

UI MeSH Term Description Entries
D010012 Osteogenesis The process of bone formation. Histogenesis of bone including ossification. Bone Formation,Ossification, Physiologic,Endochondral Ossification,Ossification,Ossification, Physiological,Osteoclastogenesis,Physiologic Ossification,Endochondral Ossifications,Ossification, Endochondral,Ossifications,Ossifications, Endochondral,Osteoclastogeneses,Physiological Ossification
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015740 Calcitonin Gene-Related Peptide A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Calcitonin Gene-Related Peptide I,Calcitonin Gene-Related Peptide II,alpha-CGRP,alpha-Calcitonin Gene-Related Peptide,beta-CGRP,beta-Calcitonin Gene-Related Peptide,Calcitonin Gene Related Peptide,Calcitonin Gene Related Peptide I,Calcitonin Gene Related Peptide II,Gene-Related Peptide, Calcitonin,alpha Calcitonin Gene Related Peptide,beta Calcitonin Gene Related Peptide
D048051 p38 Mitogen-Activated Protein Kinases A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens. Mitogen-Activated Protein Kinase p38,p38 Mitogen-Activated Protein Kinase,p38 MAP Kinase,p38 MAPK,p38 Protein Kinase,p38 SAPK,MAP Kinase, p38,MAPK, p38,Mitogen Activated Protein Kinase p38,Protein Kinase, p38,p38 Mitogen Activated Protein Kinase,p38 Mitogen Activated Protein Kinases
D059630 Mesenchymal Stem Cells Mesenchymal stem cells, also referred to as multipotent stromal cells or mesenchymal stromal cells are multipotent, non-hematopoietic adult stem cells that are present in multiple tissues, including BONE MARROW; ADIPOSE TISSUE; and WHARTON JELLY. Mesenchymal stem cells can differentiate into mesodermal lineages, such as adipocytic, osteocytic and chondrocytic. Adipose Tissue-Derived Mesenchymal Stem Cell,Adipose Tissue-Derived Mesenchymal Stromal Cell,Adipose-Derived Mesenchymal Stem Cell,Bone Marrow Mesenchymal Stem Cell,Mesenchymal Stromal Cell,Mesenchymal Stromal Cells,Multipotent Bone Marrow Stromal Cell,Multipotent Mesenchymal Stromal Cell,Adipose Tissue-Derived Mesenchymal Stem Cells,Adipose Tissue-Derived Mesenchymal Stromal Cells,Adipose-Derived Mesenchymal Stem Cells,Adipose-Derived Mesenchymal Stromal Cells,Bone Marrow Mesenchymal Stem Cells,Bone Marrow Stromal Cell,Bone Marrow Stromal Cells,Bone Marrow Stromal Cells, Multipotent,Bone Marrow Stromal Stem Cells,Mesenchymal Progenitor Cell,Mesenchymal Progenitor Cells,Mesenchymal Stem Cell,Mesenchymal Stem Cells, Adipose-Derived,Mesenchymal Stromal Cells, Multipotent,Multipotent Bone Marrow Stromal Cells,Multipotent Mesenchymal Stromal Cells,Stem Cells, Mesenchymal,Wharton Jelly Cells,Wharton's Jelly Cells,Adipose Derived Mesenchymal Stem Cell,Adipose Derived Mesenchymal Stem Cells,Adipose Derived Mesenchymal Stromal Cells,Adipose Tissue Derived Mesenchymal Stem Cell,Adipose Tissue Derived Mesenchymal Stem Cells,Adipose Tissue Derived Mesenchymal Stromal Cell,Adipose Tissue Derived Mesenchymal Stromal Cells,Mesenchymal Stem Cells, Adipose Derived,Progenitor Cell, Mesenchymal,Progenitor Cells, Mesenchymal,Stem Cell, Mesenchymal,Stromal Cell, Mesenchymal,Stromal Cells, Mesenchymal,Wharton's Jelly Cell,Whartons Jelly Cells
D020935 MAP Kinase Signaling System An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade. MAP Kinase Cascade,MAP Kinase Module,MAP Kinase Signaling Cascade,MAP Kinase Signaling Pathway,MAP Kinase Signaling Pathways,ERK Pathway,ERK Signal Tranduction Pathway,ERK1 and ERK2 Pathway,ERK1-2 Pathway,JNK Pathway,JNK Signaling Pathway,MAP Kinase Modules,MAP Kinase Signaling Cascades,MEK-ERK Pathway,p38 Kinase Pathway,p38 Kinase Signaling Pathway,Cascade, MAP Kinase,ERK Pathways,ERK1 2 Pathway,ERK1-2 Pathways,JNK Pathways,JNK Signaling Pathways,Kinase Cascade, MAP,Kinase Pathway, p38,Kinase Pathways, p38,MAP Kinase Cascades,MEK ERK Pathway,MEK-ERK Pathways,Module, MAP Kinase,Pathway, ERK,Pathway, ERK1-2,Pathway, JNK,Pathway, JNK Signaling,Pathway, MEK-ERK,Pathway, p38 Kinase,Pathways, ERK,Pathways, ERK1-2,Pathways, JNK,Pathways, JNK Signaling,Pathways, MEK-ERK,Pathways, p38 Kinase,Signaling Pathway, JNK,Signaling Pathways, JNK,p38 Kinase Pathways

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