tBHQ Suppresses Osteoclastic Resorption in Xenogeneic-Treated Dentin Matrix-Based Scaffolds

Extracellularmatrix (ECM)-based scaffolds are important for their potential therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive microenvironment for tooth root regeneration. Considering the limited sources, xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM-based scaffold presents severe osteolysis and resorption lacunae causing regenerated tooth root failure. Immune response-induced excessive osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and resorption. The impact of antioxidant, tert-butylhydroquinone (tBHQ), on xTDM/aDFCs-induced osteoclastogenesis and osteoclastic resorption in vivo and in vitro are investigated. tBHQ upregulates heme oxygenase-1 release and downregulates high mobility group box 1 mRNA expression. mRNA expression of other osteoclast-related genes including nuclear factor-kappa Bp65, receptor activator of nuclear factor kappa-B, nuclear factor of activated T-cells cytoplasmic 1, cathepsin K, and integrin β3, also decreases significantly. Furthermore, tBHQ-treated xTDM/aDFCs scaffolds implanted into rhesus macaques show reduced osteolysis and osteoclastic resorption by microcomputed tomography and tartrate-resistant acid phosphatase staining. tBHQ-induced suppression of xTDM/aDFC-induced osteoclastogenesis and osteoclastic resorption presents a new strategy for the regeneration of biological tooth root and could be applied to the regeneration of other complex tissues and organs.