Facilitating Reparative Dentin Formation Using Apigenin Local Delivery in the Exposed Pulp Cavity

Abstract

Apigenin, a natural product belonging to the flavone class, affects various cell physiologies, such as cell signaling, inflammation, proliferation, migration, and protease production. In this study, apigenin was applied to mouse molar pulp after mechanically pulpal exposure to examine the detailed function of apigenin in regulating pulpal inflammation and tertiary dentin formation. In vitro cell cultivation using human dental pulp stem cells (hDPSCs) and in vivo mice model experiments were employed to examine the effect of apigenin in the pulp and dentin regeneration. In vitro cultivation of hDPSCs with apigenin treatment upregulated bone morphogenetic protein (BMP)- and osteogenesis-related signaling molecules such as BMP2, BMP4, BMP7, bone sialoprotein (BSP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) after 14 days. After apigenin local delivery in the mice pulpal cavity, histology and cellular physiology, such as the modulation of inflammation and differentiation, were examined using histology and immunostainings. Apigenin-treated specimens showed period-altered immunolocalization patterns of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), NESTIN, and transforming growth factor (TGF)-β1 at 3 and 5 days. Moreover, the apigenin-treated group showed a facilitated dentin-bridge formation with few irregular tubules after 42 days from pulpal cavity preparation. Micro-CT images confirmed obvious dentin-bridge structures in the apigenin-treated specimens compared with the control. Apigenin facilitated the reparative dentin formation through the modulation of inflammation and the activation of signaling regulations. Therefore, apigenin would be a potential therapeutic agent for regenerating dentin in exposed pulp caused by dental caries and traumatic injury.

Localization of senescent cells under cavity preparations in rats and restoration of reparative dentin formation by senolytics

“…To date, various animal DCP models have been developed to evaluate reparative dentin formation 29,30) . These DCP models are roughly classified as pulp-exposed models 31,32) and non-pulp-exposed models 33,34) . Pulp exposure increases the risk of inducing pulp necrosis 35,36) , which potentially veils the cellular behavior of senescent cells for reparative dentin formation.…”

Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid

“…Recently, studies on ER regulation and vesicle trafficking made use of chemical chaperone treatments to subdue a range of incurable diseases ( Singh et al, 2008 ; Luo et al, 2010 ; Wu et al, 2020 ). Similarly, in this study, in order to modulate the excessive inflammatory environment and promote dentin regeneration after pulp exposure, we examined the function of the chemical chaperone 4PBA, one of the candidate drugs for relieving ER stress, an important cellular step for protein formation and secretion in regeneration, and as a drug repositioning approach, in exposed pulp cavity for 3, 5, and 42 days, using a well-established animal model system ( Jung et al, 2017 ; Aryal et al, 2021 ).…”

“…The mice were sacrificed after 3, 5, and 42 days from drug treatment for immunological and histological analyses as described previously ( Jung et al, 2017 ; Aryal et al, 2021 ). Primary antibodies were directed against NESTIN (1:400; cat.…”

“…After treatment, the exposed teeth were double-sealed with Dycal (Dentsply Caulk, Milford, DE) and light-cured composite resin with a bonding system. The drug was treated for 3, 5, and 42 days ( Jung et al, 2017 ; Aryal et al, 2021 ).…”

Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement

“…Apigenin, a natural flavonoid with strong antioxidant, and anti-inflammatory properties, could upregulate several osteogenesis-related signaling molecules, such as osteocalcin (OCN), bone sialoprotein (BSP), runt-related transcription factor 2 (RUNX2), BMP2, BMP4, and BMP7 in hDPSCs post 14 days of treatment [ 235 ]. This study also confirmed the role of apigenin in facilitating dentin-bridge formation with few irregular tubules in mice pulpal cavities after 42 days of treatment with apigenin [ 235 ]. Tanshinone IIA is a diterpene quinone derived from Salvia miltiorrhiza, and has been reported to induce hPDLSC osteogenesis via the ERK1/2-Runx2 axis signaling pathway [ 236 ].…”