title: IL-1β impedes the chondrogenic differentiation of synovial fluid mesenchymal stem cells in the human temporomandibular joint.
abstract: Mesenchymal stem cell-based therapy has great therapeutic potential for temporomandibular joint (TMJ) cartilage repair. However, the behavior of mesenchymal stem cells in the inflammatory milieu following their delivery remains poorly understood. Synovial fluid-derived mesenchymal stem cells (SFMSCs) are a promising resource for TMJ cartilage repair, as they are easily obtained from patients with TMJ disorders (TMD). In this study, we obtained SFMSCs from patients with TMD and expanded them in vitro; we then stimulated the cells with interleukin (IL)‑8, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α and IL-12p. The cells expressed CD90, CD44, CD105 and CD73, and were negative for CD45, CD34, CD11b, CD19 and HLA-DR. They could be induced to differentiate into osteogenic, chondrogenic, adipogenic and neurogenic lineages in vitro. Only the levels of IL-6 and IL-8 were upregulated significantly following stimulation with IL-8, IL-1β, IL-6, IL-10, TNF-α and IL-12p. Furthermore, IL-6 and IL-8 expression was driven mainly by IL-1β-dependent nuclear factor-κB (NF-κB) pathway activation, and was independent of IL-8, IL-6, IL-10, TNF-α and IL-12p. IL-6 and IL-8 expression was inhibited completely by treatment with the NF-κB inhibitor, BAY11-7082. SRY-box 9 (SOX9) was downregulated and matrix metalloproteinase (MMP)13 was upregulated upon chondrogenic differentiation induced in the cells also exposed to IL-1β. Sulfated glycosaminoglycan production was also reduced upon chondrogenic differentiation in the presence of IL-6, but not IL-8. Thus, IL-1β in the inflammatory milieu is crucial in regulating SFMSCs. In doing so, IL-1β impedes the chondrogenic differentiation of SFMSCs. The upregulation of IL-6 and NF-κB pathway activation also contribute to this biological behavior. The findings of our study indicate the potential adverse effects of IL-1β on the chondrogenic differentiation of SFMSCs, and may thus provide new insight into the pathogenesis of TMD.
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Yangpeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D010641:Phenotype; D015398:Signal Transduction; D013582:Synovial Fluid / Q000166:cytology*; D013704:Temporomandibular Joint
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B