通过孟德尔遗传模式研究骨关节炎和骨肉瘤的分子机制与遗传易感性

Osteoarthritis and osteosarcoma are important orthopedic diseases whose genetic susceptibility and molecular mechanisms require further investigation. This study aims to systematically analyze the genetic variation characteristics and cellular molecular networks of these two diseases through Mendelian genetic approaches.

Genome-wide association study (GWAS) was employed to identify genetic susceptibility loci for osteoarthritis, and protein-protein interaction networks were constructed to analyze key gene functions. Single-cell RNA sequencing was performed on osteosarcoma tissues, with t-SNE dimensionality reduction analysis to identify cell subpopulations and intercellular communication network analysis.

Osteoarthritis GWAS analysis revealed multiple significant peaks across 22 chromosomes, identifying genetic variant loci associated with disease susceptibility. Protein-protein interaction networks revealed functional associations among key regulatory genes including TP53, PIK3R3, AKT1, and BRCA1. Single-cell analysis of osteosarcoma successfully identified 11 cell types, including osteoblasts, chondrocytes, osteoclasts, macrophages, T cells, and B cells. Mitochondrial ribosomal protein genes of the MRPL family showed coordinated high expression in specific cell subsets, suggesting the important role of mitochondrial function in tumorigenesis. Intercellular communication analysis revealed that NK cells and B cells play central regulatory roles in the tumor immune microenvironment.

This study systematically elucidated the genetic susceptibility mechanisms of osteoarthritis and cellular heterogeneity characteristics of osteosarcoma based on Mendelian genetic principles. The findings provide important insights into understanding the genetic basis and molecular mechanisms of orthopedic diseases, laying a theoretical foundation for precision medicine and targeted therapeutic strategy development.