title: COMP-Ang1 inhibits apoptosis as well as improves the attenuated osteogenic differentiation of mesenchymal stem cells induced by advanced glycation end products.
abstract: BACKGROUND
  In the present study, we have investigated the possibility that cartilage oligomeric matrix protein angiopoietin1 (COMP-Ang1), important factor in angiogenesis, osteogenesis and the survival of mesenchymal stem cells (MSCs) through the Ang1/Tie2 pathway has beneficial effects on osteogenic differentiated cells (ODCs) from MSCs treated by advanced glycation end products (AGE), which are pathological factors of diabetes.
  
  
  METHODS
  Primary culture of MSCs was used. For comparison analysis of AGE and COMP-Ang1 effects, we performed cell viability assay with each treated variety concentration for 24h. Apoptosis rate and Caspase-3 activity were measured by each ELISA assay. To make sure with Ang1/Tie2 pathway, we performed small interfering RNA transfected to MSCs. Real-time RT-PCR was performed to identify ODCs marker genes. Immunoblotting was used to evaluate the expression of Tie2, AKT, p38 and ERK.
  
  
  RESULTS
  Our results clearly demonstrate that COMP-Ang1 upregulates the phosphorylation of AKT and p38 by activating the Ang1/Tie2 signaling pathway, indicating that COMP-Ang1 affects both AGE-induced apoptosis and the attenuated osteogenic differentiation of MSCs through the p38/MAPK and PI3K/AKT pathways.
  
  
  CONCLUSIONS
  COMP-Ang1 improves cell viability and differentiation function of ODCs against AGE via Ang/Tie2 signaling pathway.
  
  
  CONCLUSIONS
  Our results suggest the potential importance of COMP-Ang1 as a new therapy for impaired bone formation that is associated with diabetes and advanced age.
authors.affiliation: Department of Laboratory Animal Medicine, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Sokho
authors.initials: S
authors.lastname: Kim
authors.forename: Jungkee
authors.initials: J
authors.lastname: Kwon
mesh_terms: D042683:Angiopoietin-1 / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006023:Glycoproteins / Q000502:physiology*; D008297:Male; D064235:Matrilin Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D042683:Angiopoietin-1; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D064235:Matrilin Proteins
keywords: AGE; Advanced glycation end products; Ang1; Angiopoietin1; COMP; COMP-Ang1; Cartilage oligomeric matrix; Diabetes; MAPK; MSCs; Mesenchymal stem cells; Mitogen-activated protein kinase; ODCs; Osteogenic differentiated cells; PI3K; Phosphatidylinositol 3-kinase; RAGE; Receptor of advanced glycation end products; Small interfering RNA; Tie2 signaling; siRNA