National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, 610041, China.
Adv Healthc Mater. 2017 Sep;6(18). doi: 10.1002/adhm.201700127. Epub 2017 Jul 11.
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.
细胞外基质（ECM）基支架因其潜在的治疗应用而非常重要。处理牙本质基质（TDM）是一种 ECM，接种同种异体牙滤泡干细胞（TDM/aDFC）为牙根再生提供了合适的诱导微环境。考虑到来源有限，异种 TDM（xTDM）可能是同种 TDM 的替代物；然而，基于 xTDM 的支架存在严重的溶骨性和吸收性腔隙，导致再生牙根失败。免疫反应诱导的破骨细胞过度生成在异种支架溶骨性和吸收性中起着关键作用。研究了抗氧化剂叔丁基对苯二酚（tBHQ）对 xTDM/aDFC 诱导的破骨细胞生成和体内体外破骨细胞吸收的影响。tBHQ 上调血红素加氧酶-1 的释放并下调高迁移率族蛋白 1 mRNA 的表达。其他破骨细胞相关基因的 mRNA 表达，包括核因子-κBp65、核因子受体激活剂 κB、激活 T 细胞胞浆 1、组织蛋白酶 K 和整合素 β3，也显著降低。此外，用 tBHQ 处理的 xTDM/aDFC 支架植入恒河猴后，通过微计算机断层扫描和抗酒石酸酸性磷酸酶染色显示溶骨性和破骨细胞吸收减少。tBHQ 诱导的抑制 xTDM/aDFC 诱导的破骨细胞生成和破骨细胞吸收为生物牙根再生提供了一种新策略，并可应用于其他复杂组织和器官的再生。
