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Cross-Platform Transcriptomic Validation Identifies SERPINB2 as a Chondrogenic Biomarker and Reveals Coordinated Suppression of DPP4 During Cartilage Lineage Commitment

ABSTRACT: Human mesenchymal stem cells (hMSCs) are a promising source for regenerative medicine, especially mesodermal lineages. Clinical applications require an understanding of the mechanisms for transcriptional control to maintain the desired cell type. The aim of this study was to identify novel markers for differentiation of cartilage with the use of Kartogenin, by RNA analysis using microarray technology. Results: We found genes that were either up- or downregulated on differentiation, when compared to PI hMSC (control) at day 0 of differentiation. SERPINB2, was significantly upregulated in the cartilage groups,The most significant hits were validated by quantitative polymerase chain reaction

ORGANISM(S): Homo sapiens

PROVIDER: GSE325419 | GEO | 2026/03/20

REPOSITORIES: GEO

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Project description:Analysis of gene expression differences between human neonatal articular cartilage and human mesenchymal stem cells (hMSCs)-derived cartilage, to identify novel molecular signature for tissue engineered articular cartilage Abstract: Cellular differentiation comprises a progressive, multistep program that drives cells to fabricate a tissue with specific and site distinctive structural and functional properties. Cartilage constitutes one of the potential differentiation lineages that mesenchymal stem cells (MSCs) can follow under the guidance of specific bioactive agents. Single agents such as transforming growth factor beta (TGF-b) and bone morphogenetic protein 2 in unchanging culture conditions have been historically used to induce in vitro chondrogenic differentiation of MSCs. Despite the expression of traditional chon- drogenic biomarkers such as type II collagen and aggrecan, the resulting tissue represents a transient cartilage rather than an in vivo articular cartilage (AC), differing significantly in structure, chemical composition, cellular phenotypes, and mechanical properties. Moreover, there have been no comprehensive, multicomponent parameters to define high- quality and functional engineered hyaline AC. To address these issues, we have taken an innovative approach based on the molecular interrogation of human neonatal articular cartilage (hNAC), dissected from the knees of 1-month-old cadaveric specimens. Subsequently, we compared hNAC-specific transcriptional regulatory elements and differentially expressed genes with adult human bone marrow (hBM) MSC-derived three-dimensional cartilage structures formed in vitro. Using microarray analysis, the transcriptome of hNAC was found to be globally distinct from the transient, cartilage-like tissue formed by hBM-MSCs in vitro. Specifically, over 500 genes that are highly expressed in hNAC were not expressed at any time point during in vitro human MSC chondrogenesis. The analysis also showed that the differences were less variant during the initial stages (first 7 days) of the in vitro chondrogenic differentiation program. These observations suggest that the endochondral fate of hBM-MSC-derived cartilage may be rerouted at earlier stages of the TGF-b-stimulated chondrogenic differentiation program. Based on these analyses, several key molecular dif- ferences (transcription factors and coded cartilage-related proteins) were identified in hNAC that will be useful as molecular inductors and identifiers of the in vivo AC phenotype. Our findings provide a new gold standard of a molecularly defined AC phenotype that will serve as a platform to generate novel approaches for AC tissue engineering.

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Cross-Platform Transcriptomic Validation Identifies SERPINB2 as a Chondrogenic Biomarker and Reveals Coordinated Suppression of DPP4 During Cartilage Lineage Commitment

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