Gene Expression Patterns and Phenotypic Associations in Chondrogenesis: Insights into Skeletal Dysplasia Nosology

Abstract

The differentiation of mesenchymal stem cells (MSCs) into chondrocytes, known as chondrogenesis, is a complex process that plays a fundamental role in cartilage formation and skeletal development. This study elucidates the transcriptional dynamics and phenotypic correlations at various stages of chondrogenesis (early, mid, and late) using RNA-seq data. We focused on the differential expression of transcription factors (TFs) and RNA-binding proteins (RBPs). We identified critical genes during their highest expression periods and generated heatmaps to visualize these temporal patterns. Additionally, we conducted a comprehensive analysis of skeletal dysplasia nosology genes, determining their highest expression periods and phenotypic implications using the DisGeNET database. Our findings reveal that early-stage (D1) gene expression is linked to craniofacial development and limb formation anomalies, primarily involving genes responsible for extracellular matrix (ECM) organization and signal transduction. Mid-stage (D7) genes are associated with cartilage matrix composition and skeletal growth, highlighting roles in chondrocyte proliferation and matrix deposition. Late-stage (D21) genes are implicated in bone mineral density, cartilage integrity, and joint formation, ensuring the maturation and functionality of cartilage tissue. This study provides a detailed analysis of gene expression regulators and their phenotypic correlations during chondrogenesis, offering insights into the molecular mechanisms driving cartilage development and skeletal dysplasias. Understanding these temporal gene expression patterns enhances our knowledge of chondrogenesis and aids in developing targeted therapies for cartilage-related diseases. These findings underscore the significance of time-point analyses in capturing the dynamic regulation of gene expression throughout the differentiation process.