DNA synthesis of rat bone marrow mesenchymal stem cells through alpha1-adrenergic receptors

Jing Han; Zhongmin Zou; Caizhong Zhu; Jun Deng; Junping Wang; Xinze Ran; Chunmeng Shi; Guoping Ai; Rong Li; Tianmin Cheng; Yongping Su

doi:10.1016/j.abb.2009.08.009

DNA synthesis of rat bone marrow mesenchymal stem cells through alpha1-adrenergic receptors

Arch Biochem Biophys. 2009 Oct 15;490(2):96-102. doi: 10.1016/j.abb.2009.08.009. Epub 2009 Aug 18.

Authors

Jing Han¹, Zhongmin Zou, Caizhong Zhu, Jun Deng, Junping Wang, Xinze Ran, Chunmeng Shi, Guoping Ai, Rong Li, Tianmin Cheng, Yongping Su

Affiliation

¹ Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.

PMID: 19695215
DOI: 10.1016/j.abb.2009.08.009

Abstract

Multipotential bone marrow mesenchymal stem cells (BMSCs) are important in maintaining the microenvironment of the bone marrow (BM). Sympathetic nerves histologically innervate the BM; however, their role remains unclear. In this study, the effects of norepinephrine on DNA synthesis and the related signaling molecules involved in rBMSCs were examined. mRNA levels of the alpha1-adrenergic receptor subtypes increased following norepinephrine stimulation (10(-5) M for 30 min). DNA synthesis increased in dose- and time-dependent manners as determined by [(3)H]thymidine incorporation. Intracellular Ca(2+) concentration and translocation of protein kinase C from the cytosol to the membrane were also found to be elevated in rBMSCs. Phentolamine was able to suppress translocation of PKC. Norepinephrine also induced phosphorylation of ERK1/2, which was prevented by staurosporine treatment. Pretreatment with PD98059 inhibited ERK1/2 phosphorylation and DNA synthesis in rBMSCs. These findings indicate that norepinephrine stimulates DNA synthesis via alpha1-adrenergic receptors and downstream Ca(2+)/PKC and ERK1/2 activation in rBMSCs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / cytology
Adipocytes / metabolism
Animals
Base Sequence
Bone Marrow / innervation
Calcium Signaling / drug effects
Cell Differentiation
Cell Proliferation / drug effects
Cells, Cultured
DNA / biosynthesis*
DNA Primers / genetics
Flavonoids / pharmacology
Hematopoietic Stem Cells / drug effects
Hematopoietic Stem Cells / metabolism*
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Multipotent Stem Cells / drug effects
Multipotent Stem Cells / metabolism*
Norepinephrine / pharmacology
Osteoblasts / cytology
Osteoblasts / metabolism
Phentolamine / pharmacology
Protein Kinase C / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Receptors, Adrenergic, alpha-1 / genetics
Receptors, Adrenergic, alpha-1 / metabolism*

Substances

DNA Primers
Flavonoids
RNA, Messenger
Receptors, Adrenergic, alpha-1
DNA
Protein Kinase C
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Norepinephrine
Phentolamine