Molecular Crosstalk Between Osteoporosis and Osteosarcoma: Identification of Common Diagnostic Markers and Therapeutic Targets.

BACKGROUND

Osteoporosis and osteosarcoma share certain molecular pathways, and identifying common hub genes could provide new insights into their pathogenesis. This study aimed to identify and validate hub genes involved in both osteoporosis and osteosarcoma and explore their potential as biomarkers and therapeutic targets.

METHODS

We retrieved three publicly available datasets: GSE13850 (osteoporosis), GSE16088, and GSE12865 (osteosarcoma). Differentially expressed genes (DEGs) were identified using the limma package in R, and common DEGs were determined through Venn analysis. The hub genes were identified using the STRING database and Cytoscape software. Reverse transcription quantitative PCR was used to validate gene expression in osteosarcoma cell lines and normal bone tissue cell lines. Functional assays including cell proliferation, colony formation, and wound healing were conducted after CLTA and SMAD3 knockdown via small interfering RNA. Gene set enrichment, promoter methylation analysis, and genetic alteration studies were conducted using publicly available databases.

RESULTS

The hub genes identified, CLTA, MSR1, MTF2, and SMAD3, were highly expressed in osteosarcoma compared to normal controls, and their expression was validated across osteosarcoma tissue samples. Survival analysis showed that high expression of these genes correlated with poor prognosis in osteosarcoma patients. Gene enrichment analysis suggested that these genes play crucial roles in osteosarcoma development through various signaling pathways. CLTA and SMAD3 silencing in MG63 and U2OS cells led to significant reductions in cell proliferation, colony formation, and migration.

CONCLUSIONS

This study identified CLTA, MSR1, MTF2, and SMAD3 as potential biomarkers and therapeutic targets for osteoporosis and osteosarcoma. However, further studies are needed before determining clinical implications.