title: The impact of Wnt signalling and hypoxia on osteogenic and cementogenic differentiation in human periodontal ligament cells.
abstract: Cementum is a periodontal support tissue that is directly connected to the periodontal ligament. It shares common traits with bone tissues, however, unlike bone, the cementum has a limited capacity for regeneration. As a result, following damage the cementum rarely, if ever, regenerates. Periodontal ligament cells (PDLCs) are able to differentiate into osteoblastic and cementogenic lineages according to specific local environmental conditions, including hypoxia, which is induced by inflammation or activation of the Wnt signalling pathway by local loading. The interactions between the Wnt signalling pathway and hypoxia during cementogenesis are of particular interest to improve the understanding of periodontal tissue regeneration. In the present study, osteogenic and cementogenic differentiation of PDLCs was investigated under hypoxic conditions in the presence and absence of Wnt pathway activation. Protein and gene expression of the osteogenic markers type 1 collagen (COL1) and runt‑related transcription factor 2 (RUNX2), and cementum protein 1 (CEMP1) were used as markers for osteogenic and cementogenic differentiation, respectively. Wnt signalling activation inhibited cementogenesis, whereas hypoxia alone did not affect PDLC differentiation. However, hypoxia reversed the inhibition of cementogenesis that resulted from overexpression of Wnt signalling. Cross-talk between hypoxia and Wnt signalling pathways was, therefore, demonstrated to be involved in the differentiation of PDLCs to the osteogenic and cementogenic lineages. In summary, the present study suggests that the differentiation of PDLCs into osteogenic and cementogenic lineages is partially regulated by the Wnt signalling pathway and that hypoxia is also involved in this process.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Shuigen
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shao
authors.affiliation: Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Thor
authors.initials: T
authors.lastname: Friis
authors.affiliation: Department of Oral Biology and Biomaterials, Xiamen Stomatology Research Institute, Xiamen, Fujian 361000, P.R. China.
authors.forename: Jiangwu
authors.initials: J
authors.lastname: Yao
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D025021:Cementogenesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000166:cytology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D051795:Hypoxia-Inducible Factor 1, alpha Subunit