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New biomarkers for cartilage regeneration following autologous chondrocyte transplantation
The present study aimed at defining biomarkers and functional pathways for the optimization of chondrogenic differentiation in stem cell-based, autologous chondrocyte transplantation (MACT). First, biomarkers and pathways of chondrogenic differentiation were defined in cartilage regenerates after MACT/cartilage repair procedures by generating an atlas of differential gene expression between second look biopsies (2nd LB) and normal cartilage, osteoarthritis (OA) cartilage, or 3D-cultured chondrocytes using Affymetrix microarrays and bioinformatics. Target molecules/pathways were then validated by PCR and gene ontology analysis. The functional importance of the periostin-Wnt-MMP13 pathway was then addressed by silencing of periostin in OA chondrocytes and the analysis of target and phenotype genes at the mRNA and protein level. There was only limited similarity between 2nd LB and normal cartilage, indicating incomplete repair after cartilage replacement. On the other hand, similarities between 2nd LB and OA cartilage concerning the expression of inflammatory response genes suggested a contribution of inflammatory processes to the incomplete defect healing. Also, the overexpression of matrix degradation and mis-differentiation markers (including the periostin-Wnt-MMP13 pathway), indicated molecular abnormalities during insufficient cartilage repair. As a proof of concept, successful silencing of periostin in OA chondrocytes resulted in transient downregulation of tissue-degrading MMP13 (mRNA and protein) and in upregulation of cartilage-specific collagen 2, pointing to favorable effects of periostin silencing on the chondrogenic phenotype and the formation of mature cartilage. Transient upregulation of the wound healing markers ICAM 1 and collagen 3, however, indicated that periostin silencing may concurrently augment the formation of scar tissue, requiring further refinement of the therapeutic molecular targets. ; Ziel der aktuellen Studie war die Definition von Biomarkern und funktionellen Signalwegen zur ...
New biomarkers for cartilage regeneration following autologous chondrocyte transplantation
The present study aimed at defining biomarkers and functional pathways for the optimization of chondrogenic differentiation in stem cell-based, autologous chondrocyte transplantation (MACT). First, biomarkers and pathways of chondrogenic differentiation were defined in cartilage regenerates after MACT/cartilage repair procedures by generating an atlas of differential gene expression between second look biopsies (2nd LB) and normal cartilage, osteoarthritis (OA) cartilage, or 3D-cultured chondrocytes using Affymetrix microarrays and bioinformatics. Target molecules/pathways were then validated by PCR and gene ontology analysis. The functional importance of the periostin-Wnt-MMP13 pathway was then addressed by silencing of periostin in OA chondrocytes and the analysis of target and phenotype genes at the mRNA and protein level. There was only limited similarity between 2nd LB and normal cartilage, indicating incomplete repair after cartilage replacement. On the other hand, similarities between 2nd LB and OA cartilage concerning the expression of inflammatory response genes suggested a contribution of inflammatory processes to the incomplete defect healing. Also, the overexpression of matrix degradation and mis-differentiation markers (including the periostin-Wnt-MMP13 pathway), indicated molecular abnormalities during insufficient cartilage repair. As a proof of concept, successful silencing of periostin in OA chondrocytes resulted in transient downregulation of tissue-degrading MMP13 (mRNA and protein) and in upregulation of cartilage-specific collagen 2, pointing to favorable effects of periostin silencing on the chondrogenic phenotype and the formation of mature cartilage. Transient upregulation of the wound healing markers ICAM 1 and collagen 3, however, indicated that periostin silencing may concurrently augment the formation of scar tissue, requiring further refinement of the therapeutic molecular targets. ; Ziel der aktuellen Studie war die Definition von Biomarkern und funktionellen Signalwegen zur ...
New biomarkers for cartilage regeneration following autologous chondrocyte transplantation
Kalla, Pavan Kumar (Autor:in) / Kinne, Raimund W. / Wetzker, Reinhard / Sittinger, Michael
01.01.2019
Hochschulschrift
Elektronische Ressource
Englisch
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