Dextrose prolotherapy at varying concentrations ameliorates tendon injury via IGF-2R: an integrated study of Mendelian randomization and an animal model.

BACKGROUND

This study integrates Mendelian randomization (MR) analysis with animal experiments to systematically evaluate the therapeutic efficacy of varying concentrations of hypertonic dextrose on tendon injury and elucidate the underlying mechanisms in the context of tendon repair.

METHODS

The SwissTargetPrediction database was utilized to identify potential molecular targets of dextrose. Two-sample MR analysis was performed to investigate the causal relationships between the identified targets and Achilles tendinopathy. Comprehensive in vivo experiments that included behavioral tests, histological examination (hematoxylin‒eosin staining), and molecular analyses (Western blotting and RT‒qPCR) were conducted to validate the MR findings.

RESULTS

MR analysis revealed a significant causal association between dextrose-mediated effects and IGF-2R expression in the context of Achilles tendinopathy. In vivo studies demonstrated that tendon injury significantly impaired motor function in a rat model, with notable improvements observed after dextrose intervention. Histopathological analysis revealed that injured tendons presented disorganized collagen fiber arrangement, enhanced neovascularization, and increased cellular proliferation. Dextrose treatment at both 15% and 25% concentrations significantly improved collagen fiber organization, resulting in more compact and parallel fiber alignment. Furthermore, dextrose intervention significantly modulated the expression of molecular markers, including reduced type III collagen expression, upregulated vascular endothelial growth factor expression, and downregulated IGF-2R mRNA expression. Notably, 25% dextrose solution demonstrated superior efficacy, significantly increasing the expression of SCX, type I collagen, and transforming growth factor-β1.

CONCLUSION

Hypertonic dextrose downregulates IGF-2R expression, upregulates vascular endothelial growth factor and transforming growth factor-β1 expression, modulates collagen synthesis, increases type I collagen content, and accelerates tendon healing. Among the tested concentrations, 25% hypertonic glucose yielded the best therapeutic outcomes.