Document Detail

Reversine enhances generation of progenitor-like cells by dedifferentiation of annulus fibrosus cells.
MedLine Citation:
PMID:  19947906     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to determine if treatment with reversine, a purine analog, promoted generation of skeletal progenitor cells from lineage-committed annulus fibrosus cells. Reversine modulated cell growth, morphology, and the actin cytoskeleton of annulus fibrosus cells. Microarray profiling coupled with Ingenuity Pathway Analysis revealed that reversine treatment resulted in a significant expression change in many genes including those required for cell-cell interaction, cell movement, cell growth, and development. Further analysis revealed that there was involvement of gene networks concerned with cellular assembly and organization, DNA replication and repair, tissue morphology, and cell-to-cell signaling. The gene expression profile was dependent on reversine concentration. In osteogenic media, cells pretreated with 300 nM reversine exhibited an increased induction in alkaline phosphatase activity and enhanced expression of alkaline phosphatase, bone sialoprotein, osteocalcin, and collagen type I mRNA. Maintained in adipogenic media, the reversine-pretreated annulus cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of PPAR-gamma2, LPL, and Fabp mRNA. In chondrogenic media, cells pretreated with reversine exhibited marked increase in the induction of aggrecan, collagen types II, IX, and XI, and versican. It is concluded that reversine treatment induced annulus fibrosus cell plasticity and promoted their differentiation along mesenchymal lineages. This agent could be used to generate skeletal progenitor cells to orchestrate the repair of the intervertebral disc.
Mansi Saraiya; Rena Nasser; Yan Zeng; Sankar Addya; Ravi Kumar Ponnappan; Paolo Fortina; David Greg Anderson; Todd J Albert; Irving M Shapiro; Makarand V Risbud
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  16     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-06     Completed Date:  2010-07-02     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1443-55     Citation Subset:  IM    
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MeSH Terms
Adipogenesis / drug effects,  genetics
Adult Stem Cells / cytology,  drug effects,  metabolism
Alkaline Phosphatase / metabolism
Cell Dedifferentiation / drug effects*,  genetics
Collagen / metabolism
Gene Expression Profiling
Gene Regulatory Networks / drug effects
Intervertebral Disc / cytology*,  drug effects*,  injuries
Morpholines / pharmacology*
Multipotent Stem Cells / cytology,  drug effects,  metabolism
Muscle Development / drug effects,  genetics
Myoblasts, Skeletal / cytology*,  drug effects*,  metabolism
Oligonucleotide Array Sequence Analysis
Osteogenesis / drug effects,  genetics
Purines / pharmacology*
Rats, Wistar
Tissue Engineering / methods
Grant Support
Reg. No./Substance:
0/Morpholines; 0/Purines; 9007-34-5/Collagen; EC Phosphatase; Z499CLJ023/2-(4-morpholinoanilino)-6-cyclohexylaminopurine

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