PMID- 32973567 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240329 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 11 DP - 2020 TI - Potential Application of Human beta-Defensin 4 in Dental Pulp Repair. PG - 1077 LID - 10.3389/fphys.2020.01077 [doi] LID - 1077 AB - When pulp tissue is damaged by caries or trauma, vital pulp therapy (VPT) can help preserve the pulp tissue for long-term retention of teeth. However, the choice of pulp capping agent used in VPT is important for the successful preservation of the pulp tissue. Here we investigated the expression and biological function of human beta-defensin 4 (HBD4) in dental pulp stem cells (DPSC) and explored its potential as a pulp capping agent. We examined the expression of HBD4 in DPSC in vitro using qPCR and immunofluorescence staining. We also looked at the effect of HBD4 on inflammatory factors in lipopolysaccharide (LPS)-stimulated DPSC, and its effects on mineralizing cell phenotype differentiation, via qPCR and western blot. Finally, we examined the ability of HBD4 to promote the restoration of the pulp-dentin complex in vivo, using male Wistar rats with reversible pulpitis. We found HBD4 was highly expressed in DPSC stimulated by TNF-alpha and IL-1alpha. HBD4 down-regulated the expression of inflammatory mediators (i.e., IL-1alpha, IL-1beta, IL-6, TNF-alpha) in LPS-stimulated DPSC, and suppressed MAPK activity and the NF-kappaB pathway. HBD4 also enhanced the differentiation of DPSC into osteoblasts or odontoblasts, potentially by modulating the Notch pathway. Furthermore, HBD4 controlled the degree of pulp inflammation in a rat model of reversible pulpitis and induced the formation of restorative dentin. Together our findings indicate HBD4 may be a useful pulp capping agent for use in VPT. CI - Copyright (c) 2020 Zhai, Yuan, Zhao, Ge and Wang. FAU - Zhai, Yue AU - Zhai Y AD - Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. FAU - Yuan, Xiaojing AU - Yuan X AD - Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. FAU - Zhao, Yuming AU - Zhao Y AD - Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. FAU - Ge, Lihong AU - Ge L AD - Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. FAU - Wang, Yuanyuan AU - Wang Y AD - Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. LA - eng PT - Journal Article DEP - 20200821 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC7472722 OTO - NOTNLM OT - anti-inflammatory OT - dental pulp stem cells OT - human beta-defensin 4 OT - stem cell differentiation OT - vital pulp therapy EDAT- 2020/09/26 06:00 MHDA- 2020/09/26 06:01 PMCR- 2020/08/21 CRDT- 2020/09/25 06:01 PHST- 2020/05/28 00:00 [received] PHST- 2020/08/05 00:00 [accepted] PHST- 2020/09/25 06:01 [entrez] PHST- 2020/09/26 06:00 [pubmed] PHST- 2020/09/26 06:01 [medline] PHST- 2020/08/21 00:00 [pmc-release] AID - 10.3389/fphys.2020.01077 [doi] PST - epublish SO - Front Physiol. 2020 Aug 21;11:1077. doi: 10.3389/fphys.2020.01077. eCollection 2020.