title: Formation of bone-like tissue by dental follicle cells co-cultured with dental papilla cells.
abstract: During tooth root formation, dental follicle cells (DFCs) differentiate into osteoblasts/cementoblasts when they are in contact with pre-existing dentin. Since some factors of dentin matrix were also produced by dental papilla cells (DPCs) and could induce DFCs differentiation, we hypothesized that DPCs can directly promote DFCs differentiation and that differentiation could occur in a co-culture model. To test this hypothesis, we investigated the characteristics of DFCs that are influenced by DPCs in an in vitro co-culture and in vivo heterotopic transplant model. One week into the co-culture, there were significant increases in the mRNA level of bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG), bone sialoprotein (BSP) and osteocalcin (OCN), and a decrease of the receptor activator of nuclear factor κB ligand (RANKL). Additionally, the number of BMP2-, OPG-, BSP- and OCN-positive DFCs increased whereas RANKL-positive DFCs decreased. Three weeks after co-culture, DFCs produced calcified nodules, accompanied with increased sub-cellular organelles for protein synthesis and secretion. In the heterotopic transplant model, the adult male rats were used as hosts, DFCs were transplanted into the omentum. In vivo 5-week growth of DFCs in the presence of DPCs led to the formation of bone-like tissues, positive for BSP, OCN and BMP2. In contrast, DFCs alone led to fibrous-like tissues. These results indicated that in the absence of pre-existing dentin, DPCs can stimulate osteogenesis and inhibit osteoclastogenesis in DFCs and suggested a novel strategy to promote DFCs differentiation.
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, China.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Bai
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Bai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuzaka
authors.forename: Sadamitsu
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Eitoyo
authors.initials: E
authors.lastname: Kokubu
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D025021:Cementogenesis / Q000187:drug effects* / Q000502:physiology; D018920:Coculture Techniques; D003739:Dental Cementum / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D003771:Dental Papilla / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D003795:Dental Sac / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008297:Male; D009852:Omentum / Q000601:surgery; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin