title: Wnt/β-catenin pathway regulates cementogenic differentiation of adipose tissue-deprived stem cells in dental follicle cell-conditioned medium.
abstract: The formation and attachment of new cementum is crucial for periodontium regeneration. Tissue engineering is currently explored to achieve complete, reliable and reproducible regeneration of the periodontium. The capacity of multipotency and self-renewal makes adipose tissue-deprived stem cells (ADSCs) an excellent cell source for tissue regeneration and repair. After rat ADSCs were cultured in dental follicle cell-conditioned medium (DFC-CM) supplemented with DKK-1, an inhibitor of the Wnt pathway, followed by 7 days of induction, they exhibited several phenotypic characteristics of cementoblast lineages, as indicated by upregulated expression levels of CAP, ALP, BSP and OPN mRNA, and accelerated expression of BSP and CAP proteins. The Wnt/β-catenin signaling pathway controls differentiation of stem cells by regulating the expression of target genes. Cementoblasts share phenotypical features with osteoblasts. In this study, we demonstrated that culturing ADSCs in DFC-CM supplemented with DKK-1 results in inhibition of β-catenin nuclear translocation and down-regulates TCF-4 and LEF-1 mRNA expression levels. We also found that DKK-1 could promote cementogenic differentiation of ADSCs, which was evident by the up-regulation of CAP, ALP, BSP and OPN gene expressions. On the other hand, culturing ADSCs in DFC-CM supplemented with 100 ng/mL Wnt3a, which activates the Wnt/β-catenin pathway, abrogated this effect. Taken together, our study indicates that the Wnt/β-catenin signaling pathway plays an important role in regulating cementogenic differentiation of ADSCs cultured in DFC-CM. These results raise the possibility of using ADSCs for periodontal regeneration by modifying the Wnt/β-catenin pathway.
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China; Department of Stomatology, Chinese PLA 15 Hospital, Lanzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Stomatology, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Manjing
authors.initials: M
authors.lastname: Deng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D025021:Cementogenesis / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003795:Dental Sac / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned