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

Abstract

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.

Proteomics and N‐glycoproteomics analysis of an extracellular matrix‐based scaffold‐human treated dentin matrix

“…TDM is a bioactive scaffold that derives from native dentin and retains the porous structure and functional proteins. Numerous studies have documented TDM potential for tooth root or dentin reconstruction/regeneration (Chen et al, ; Chen et al, ; Guo et al, ; Ji et al, ; Jiao et al, ; Li et al, ; Li, Sun, et al, ; Luo et al, ; Luo et al, ; Sun et al, ; Yang et al, ). Previously, studies found that TDM released several dentinogenesis‐related factors such as biglycan, collagen‐1, decorin, DMP‐1, DSP, and TGF‐β1 (Jiao et al, ; Li et al, ).…”

“…ECM‐based biomaterials can be produced from almost any tissue in the body, such as the bladder (Dahms, Piechota, Dahiya, Lue, & Tanagho, ), blood vessels (Dahl, Koh, Prabhakar, & Niklason, ), bone (Frohlich et al, ), dermis (Reing et al, ), heart valves (Rieder et al, ), kidney (Nakayama, Batchelder, Lee, & Tarantal, ), ligaments (Woods & Gratzer, ), liver (Uygun et al, ), nerves (Hudson et al, ), skeletal muscle (Conconi et al, ), small intestinal submucosa (Badylak et al, ), and tendons (Ning et al, ). Furthermore, our previous studies described the use of treated dentin matrix (TDM), a natural ECM‐based scaffold, for tooth root regeneration (Guo et al, ; Li et al, ; Sun et al, ; Yang et al, ). By a gradient ethylene diamine tetra‐acetic acid (EDTA) demineralization treatment, dentin tubules were exposed and allows releasement of odontogenic factors, which makes TDM a bioactive scaffold (Li et al, ).…”

Dental Follicle Cells: Roles in Development and Beyond

“…Considering the scant sources of allogeneic TDM (aTDM), xenogeneic TDM (xTDM) was a possible substitute for aTDM but it caused osteolysis and resorption lacunae and led to regenerated root failure. The tert -butylhydroquinone ( t BHQ), an antioxidant, can reduce osteolysis and osteoclastic resorption when added in xTDM/aDFCs scaffolds [154].…”

Application of Tissue Engineering in Tooth: A Review on Recent Trends and Advances

“…Dental follicle stem cells (DFSCs), as clonogenic cells, also have the ability of multilineage differentiation and could differentiate into cementoblasts, neural-like cells, membrane-like structures and periodontal ligament(PDL)like tissue [11][12][13][14]. And a novel method for biological tooth root regeneration was reported, which apply tertbutylhydroquinone (tBHQ) treatment of scaffolds, derived from treated dentin matrix (TDM) that is seeded with allogeneic dental follicle stem cells (TDM/aDFC) to prevent osteoclastic resorption and produce a tooth root [15]. So DFSCs seem to be a promising choice to restore a tooth root.…”