SMAD7 as a hub regulator in the pathophysiology of bone autograft healing and specific siRNA design: An in silico study

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AYDEĞER C.

Journal of advances in vetbio science and techniques, cilt.0, sa.1, ss.15-23, 2026 (TRDizin)

Özet

Bone autograft healing is a complex process requiring the coordinated regulation of multiple cellular and molecular mechanisms. Balanced activation of BMP2/TGF-β signaling pathways is critical for successful bone regeneration, and dysregulation of negative regulators within these pathways results in autograft non-union. The aim of this study was to identify a central regulatory target that suppresses BMP2/TGF-β signaling in the pathophysiology of bone autograft healing using in silico approaches and to design and prioritize specific siRNA candidates against this hub inhibitor. Gene ontology and pathway enrichment analyses were performed to evaluate inhibitors associated with BMP2/TGF-β signaling, revealing SMAD7 as the hub regulator with the highest degree of network connectivity. Subsequently, siRNA candidates targeting SMAD7 were predicted and filtered using the Ui-Tei, Reynolds, and Amarzguioui algorithms. Then one candidate was excluded due to the siExplorer score. The thermodynamic results showed that siRNA1 and siRNA3 were capable of forming stable hybrid complexes. Although both siRNAs have acceptable docking scores (−326.17 and -290.96) and a confidence score (0.9713 and 0.9437), comparative evaluation indicated that siRNA1 is determined as a primer candidate. Based on these findings, siRNA1-based approaches could be promising in bone autograft healing after in vitro and in vivo experiments are verified.