Druggable gene and single cell analyses reveal potential therapeutic targets for osteoporosis

doi:10.12307/2026.383

Abstract

Abstract: BACKGROUND: Genetic factors play an important role in the pathophysiology of osteoporosis, and Mendelian randomization can be used to infer causal associations between specific genes and diseases using eQTLs.
OBJECTIVE: To identify potential therapeutic targets for osteoporosis based on druggable genes-related Mendelian randomization and colocalization analysis, to explore the potential biological mechanisms in the treatment of osteoporosis using bioinformatics analysis, and to predict the binding activity of drug targets using drug enrichment analysis and molecular docking.
METHODS: (1) Data sources: Druggable genes were sourced from the DGIdb database (a public database constructed by the University of Washington School of Medicine, widely used for drug target discovery) and information provided in the literature. Expression quantitative trait locus (eQTL) data for druggable genes were obtained from eQTLGen (a large-scale blood eQTL database jointly constructed by multiple international research institutions, including the University of Groningen in the Netherlands). The genome-wide association study data for osteoporosis were obtained from FinnGen R12 (a large-scale genomic database led by the University of Helsinki in Finland), including 10 461 osteoporosis cases and 473 264 controls. GSE230665 chip dataset and GSE169396 single-cell dataset were obtained from the GEO database. (2) Methods: Genes closely associated with osteoporosis were screened. Gene expression specific to osteoporosis was evaluated using array. Single-cell analysis was used to further examine the regulatory role of these genes in cell communication. Additionally, enrichment analysis was performed to elucidate biological functions, and a protein-protein interaction network was constructed to analyze potential associations. Drug enrichment and molecular docking were used to predict and simulate the binding of small molecule drugs with targets.
RESULTS AND CONCLUSION: This study identified 37 druggable genes associated with osteoporosis, among which Troponin C2 and CXC chemokine receptor 6 have protective roles in osteoporosis and share causal genetic variations with the disease. Array data analysis showed that CXC chemokine receptor 6 expression was significantly reduced in osteoporosis compared with the normal group, suggesting its diminished protective role in osteoporosis. Single cell analysis further revealed that CXC chemokine receptor 6is predominantly expressed on T cells, and CXC chemokine receptor 6 positive T cells exhibit stronger cell communication abilities. Drug enrichment found that NSC95397 can target and bind CXC chemokine receptor 6, and molecular docking showed good binding activity with CXC chemokine receptor 6. These findings not only provide clues for the development of novel osteoporosis drugs but also promote the translation and application of research outcomes.

Key words: osteoporosis, Mendelian randomization, CXC chemokine receptor 6, drug targets, genes, bioinformatics analysis, single-cell analysis, genetic tissue engineering

CLC Number:

Li Yiwei, Luo Zongming, Rong Yifa, Jiang Kai, Zhang Jiahao, Lu Bowen, Li Gang. Druggable gene and single cell analyses reveal potential therapeutic targets for osteoporosis[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(25): 6654-6660.

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