RRC ID 61956
Author Tsuru M, Soejima T, Shiba N, Kimura K, Sato K, Toyama Y, Nagata K.
Title Proline/arginine-rich end leucine-rich repeat protein converts stem cells to ligament tissue and Zn(II) influences its nuclear expression.
Journal Stem Cells Dev
Abstract Our objective was to facilitate ligament tissue reconstruction by characterizing the mechanism of expression of ligament tissue. To accomplish this, we searched for proteins specific to the tissue and introduced them into mesenchymal stem cells. In the two-dimensional phosphorescent gel electrophoresis, the spots in common with the normal human ligament tissue were selected after removing the spots of the normal bone tissue from those of the ossified tissue in the spinal ligament. Proline/arginine-rich end leucine-rich repeat protein (PRELP) was identified in ligament-specific locations by liquid chromatography-tandem mass spectrometry. Transfection of PRELP into mouse mesenchymal stem cells yielded ligament-like connective tissue comprised of parallel fibers. Thus, expression of the PRELP protein could reconstruct the ligament tissue. Since zinc-related proteins were found with high incidence as a result of an array analysis of PRELP's ProtoArray, it was considered that there is a relationship to the zinc metabolism. Tissue induction was mediated by the tumor necrosis factor (TNF)-α via the zinc pathway. PRELP may be a useful gene in syndesmoplasty, provided zinc is present for tissue reconstruction. Chromosome division becomes active with the addition of zinc, and rapid tissue induction takes place in the presence of zinc and TNF-α. Currently, the reconstruction of a ruptured ligament tissue is difficult, but we expect that the PRELP protein expression may facilitate this process. This study describes the discovery of the gene responsible for the differentiation of stem cells into ligament tissue. This important finding may lead to treatments for gonarthrosis, cruciate ligament, and periodontal ligament ruptures, and ossification of the posterior longitudinal ligament.
Volume 22(14)
Pages 2057-70
Published 2013-7-15
DOI 10.1089/scd.2012.0695
PMID 23442027
MeSH Animals Cell Differentiation Chlorides / metabolism Chlorides / pharmacology* Extracellular Matrix Proteins / genetics* Extracellular Matrix Proteins / metabolism Gene Expression Gene Expression Profiling Glycoproteins / genetics* Glycoproteins / metabolism Humans Ligaments / metabolism* Ligaments / pathology Mesenchymal Stem Cells / cytology* Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / metabolism* Mice Ossification of Posterior Longitudinal Ligament / genetics* Ossification of Posterior Longitudinal Ligament / pathology Ossification of Posterior Longitudinal Ligament / physiopathology Ossification of Posterior Longitudinal Ligament / therapy Protein Array Analysis Regeneration / physiology Transfection Tumor Necrosis Factor-alpha / pharmacology Zinc Compounds / metabolism Zinc Compounds / pharmacology*
IF 3.153
Human and Animal Cells MC3T3-E1(RCB1126)