title: Double-edged-sword effect of IL-1β on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways.
abstract: Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1β (IL-1β) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1β activate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1β inhibit BMP/Smad signaling through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-κB, MAPK and BMP/Smad signaling mediates this dual effect of IL-1β on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.
authors.affiliation: Department of Prosthodontics, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Mao
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: Y-G
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Department of Prosthodontics, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: T-T
authors.initials: TT
authors.lastname: Tang
authors.affiliation: Department of Prosthodontics, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: E-Y
authors.initials: EY
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D001641:Bicuspid / Q000166:cytology / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction; D051898:Smad1 Protein / Q000235:genetics* / Q000378:metabolism; D014081:Tooth Extraction; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases