title: NOD2 Mediates Odontoblast Differentiation and RANKL Expression.
abstract: The precise regulation of odontoblast differentiation and osteoclastogenic cytokine expression in human dental pulp cells (HDPCs) is crucial for the pathology of bacteria-related pulpitis. Although the up-regulation of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) has been reported in inflamed human dental pulps, the role of NOD2 in the differentiation of HDPCs remains unclear. Here, we show the involvement of NOD2 in odontoblast differentiation together with osteoclastogenic cytokine expression in HDPCs. Treatment with muramyl dipeptide (MDP), a known NOD2-agonist, significantly inhibited odontoblast differentiation of HDPCs, as revealed by reduced ALP activity, osteoblast/odontoblast marker expression, and mineralized nodule formation. Importantly, the forced down-regulation of NOD2 by small interfering RNA (siRNA) recovered MDP-down-regulated odontoblast differentiation. MDP-elicited suppression of odontoblast differentiation resulted from the increased expression of MKP-1 protein and the subsequent decline of MAPKs phosphorylation, which is a prerequisite for odontoblast differentiation. Furthermore, we found that MDP treatment elevated the expression of osteoclastogenic cytokines in HDPCs, which was also reversed by NOD2 silencing. Analysis of these data, taken together, suggests that the regulation of NOD2 expression upon MDP challenge might serve as an intrinsic mechanism that underlies the hindered dentin formation and accelerated dentin resorption in bacterial infection-mediated pulpitis.
authors.affiliation: Department of Dental Hygiene, School of Health Science, Dankook University, Cheonan, Republic of Korea Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: S-I
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: G-T
authors.initials: GT
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea eckim@khu.ac.kr.
authors.forename: E-C
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology; D054638:Dual Specificity Phosphatase 1 / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D009804:Odontoblasts / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin / Q000187:drug effects; D053245:RANK Ligand / Q000032:analysis* / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D053244:Osteoprotegerin; D053245:RANK Ligand; D034741:RNA, Small Interfering; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D016173:Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: Map kinase phosphatase 1; dental pulp; muramyl dipeptide; osteoblasts; osteoclasts; pulpitis