Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells

Huang, Haiyun; Zhao, Ning; Xu, Xin; Xu, Yingjie; Li, Shuang; Zhang, J.; Yang, Pishan

doi:10.1111/j.1365-2184.2011.00769.x

Cited by 165 publications

(148 citation statements)

References 33 publications

(45 reference statements)

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“…The process of bone formation involves a balance between osteoblast and osteoclast activity and the healing of fractures requires a large number of osteoblasts (6). It has been demonstrated that there is a link between osteoclasts and inflammatory cytokines: High numbers of osteoclasts are associated with high numbers of inflammatory cytokines, including TNF-α and IL-1, following bone fracture (7).…”

Section: Introductionmentioning

confidence: 99%

N‑methyl pyrrolidone promotes ankle fracture healing by inhibiting inflammation via suppression of the mitogen‑activated protein kinase signaling pathway

et al. 2018

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Abstract. N-methyl pyrrolidone (NMP), a small bioactive molecule, has the potential to stimulate bone formation and inhibit osteoclast differentiation. The aim of the present study was to investigate the effect of NMP on the inflammatory response and underlying molecular mechanisms in MG-63 cells. The mRNA and protein expression of cytokines from peripheral blood in children with or without ankle fracture were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively. MG-63 cells were pre-treated with/without NMP and stimulated with 1 µM bradykinin (BK). The production of cytokines from MG-63 cells was assessed by western blotting and RT-qPCR. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein were measured using western blotting and/or RT-qPCR. Western blotting was used to examine the activation level of mitogen activated protein kinase. Compared with healthy children, levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6 mRNA and protein were upregulated in children with ankle fracture. NMP treatment did not induce cytotoxicity in MG-63 cells. The BK-induced upregulation of TNF-α, IL-1β, IL-6, iNOS and COX-2 mRNA and protein was reversed in a dose-dependent manner by NMP. Furthermore, NMP downregulated the activation of c-Jun NH2-terminal kinase and p38 pathways, but not the extracellular signal-related kinase pathway. Therefore, the results of the current study demonstrate that NMP inhibits inflammation dependent on the mitogen-activated protein kinase pathway in MG-63 cells, indicating that it may be beneficial in the healing of fractures.

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Section: Introductionmentioning

confidence: 99%

N‑methyl pyrrolidone promotes ankle fracture healing by inhibiting inflammation via suppression of the mitogen‑activated protein kinase signaling pathway

et al. 2018

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“…Both TNF-and IFN-inhibited MSC osteogenic ability in dose-dependent manner in vitro (180). Interestingly, an in vitro exposure to IFN-augmented TNF--mediated apoptosis of BM MSCs and suppressed their osteogenic differentiation (182,191). The IFN--mediated inhibition of osteogenesis of MSCs was associated with increased expression levels of SMAD-6, a negative controller of bone differentiation (182).…”

Section: Cytokinesmentioning

confidence: 93%

“…In chronic inflammatory milieu, TNF-suppresses the biomarkers of MSC osteogenic differentiation via NF-signalling-dependent mechanism (191). An exposure of mouse…”

Section: Cytokinesmentioning

confidence: 99%

Interactions Between Multipotential Stromal Cells (MSCs) and Immune Cells During Bone Healing

El-Jawhari

Jones

McGonagle

et al. 2016

Recent Advances in Stem Cells

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Abstract:The physiological process of bone healing takes place in three sequential stages: inflammation, repair and remodelling. Multipotential stromal cells (MSCs) are the key progenitor cells for osteoblasts and chondrocytes and are also imbued with immunomodulatory capabilities.Although MSCs are well known to be involved in osteogenesis during the later stages of repair, their role during the inflammatory phase and precise interactions with immune cells remain poorly understood. This chapter describes the current knowledge on cellular interactions during the bone repair as well as cytokines and growth factors mediating these processes. The roles of emerging innate immune cell populations, innate lymphoid cells are also discussed.Based on this current knowledge, we conclude that in addition to their differentiation during later bone repair stages, MSCs are likely to have a substantial involvement in the initial stage of bone healing by controlling the fate of inflammation. An improved understanding of complex cell interactions during bone repair has broad implications on optimising the treatment of the fracture complications including non-union.

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“…Several studies have proven that inflammatory cytokines IFN-g and TNF-a can block the osteogenic differentiation of MSCs [115,116]. TNF-a also works to enhance the expression of Wnt signalling pathway antagonist, Dickkopf-1 (DKK-1) that has an inhibitory effect on the osteoblast formation [117] and inhibits nephronectin, an extracellular matrix protein, which helps the proliferation of osteoblasts [118].…”

Section: The Uncontrolled Immune Cell Response and Defective Bone Heamentioning

confidence: 99%

The roles of immune cells in bone healing; what we know, do not know and future perspectives

El-Jawhari

Jones

Giannoudis

2016

Injury

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Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells

Abstract: The binding of TNF-α to its receptors results in the activation of multiple signaling pathways, which actively interact with each other to regulate the differentiation, proliferation, survival and apoptosis of MSCs.

Cited by 165 publications

References 33 publications

N‑methyl pyrrolidone promotes ankle fracture healing by inhibiting inflammation via suppression of the mitogen‑activated protein kinase signaling pathway

N‑methyl pyrrolidone promotes ankle fracture healing by inhibiting inflammation via suppression of the mitogen‑activated protein kinase signaling pathway

Interactions Between Multipotential Stromal Cells (MSCs) and Immune Cells During Bone Healing

The roles of immune cells in bone healing; what we know, do not know and future perspectives

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