Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells.
ABSTRACT To investigate tumor necrosis factor alpha (TNF-α)-induced changes in osteogenic differentiation from mesenchymal stem cells (MSCs).
Blockade of nuclear factor-κB (NF-κB) was achieved in ST2 murine MSCs via overexpression of the NF-κB inhibitor, IκBα. Osteogenic differentiation was induced in IκBα-overexpressing ST2 cells and normal ST2 cells when these cells were treated with TNF-α at various concentrations. Expression levels of bone marker genes were determined using real time RT-PCR and ALP activity assay. In vitro mineralization was performed to determine long-term exposure to TNF-α on mineral nodule formation. MTT assay was used to determine the changes in cell proliferation/survival.
Levels of Runx2, Osx, OC and ALP were up-regulated in cell cultures treated with TNF-α at lower concentrations, while down-regulated in cell cultures treated with TNF-α at higher concentrations. Blockade of NF-κB signaling reversed the inhibitory effect observed in cell cultures treated with TNF-α at higher concentrations, but showed no effect on cell cultures treated with TNF-α at lower concentrations. In contrast, long-term treatment of TNF-α at all concentrations induced inhibitory effects on in vitro mineral nodule formation. MTT assay showed that TNF-α inhibits proliferation/survival of mesenchymal stem cells when the NF-κB signaling pathway is blocked.
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.
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ABSTRACT: Bone tissue engineering is one of the important therapeutic approaches to the regeneration of bones in the entire field of regeneration medicine. Mesenchymal stem cells (MSCs) are actively discussed as material for bone tissue engineering due to their ability to differentiate into autologous bone. MSCs are able to differentiate into different lineages: osteo/odontogenic, adipogenic, and neurogenic. The tissue of origin for MSCs defines them as bone marrow-derived stem cells, adipose tissue-derived stem cells, and, among many others, dental stem cells. According to the tissue of origin, DSCs are further stratified into dental pulp stem cells, periodontal ligament stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, and dental papilla cells. There are numerous in vitro/in vivo reports suggesting successful mineralization potential or osteo/odontogenic ability of MSCs. Still, there is further need for the optimization of MSCs-based tissue engineering methods, and the introduction of genes related to osteo/odontogenic differentiation into MSCs might aid in the process. In this review, articles that reported enhanced osteo/odontogenic differentiation with gene introduction into MSCs will be discussed to provide a background for successful bone tissue engineering using MSCs with artificially introduced genes.Journal of the Korean Association of Oral and Maxillofacial Surgeons. 04/2013; 39(2):55-62.
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ABSTRACT: Rheumatoid arthritis (RA) is characterized by defective bone repair and excessive destruction and ankylosing spondylitis (AS) by increased ectopic bone formation with syndesmophytes. Since TNF-α and IL-17A are involved in both diseases, this study investigated their effects on the osteogenic differentiation of isolated human bone marrow-derived mesenchymal stem cells (hMSCs).Frontiers in Immunology 09/2014; 5:425.
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ABSTRACT: Tumor necrosis factor-α (TNF-α) plays an essential role in the regulation of bone homeostasis in several chronic immune and inflammatory joint diseases, where inhibition of TNF has led to significant clinical improvement. However, TNF-activated pathways and mechanisms involved in bone remodeling remain unclear. So far, TNF-α was known as an inhibitor of osteoblast differentiation and an activator of osteoclastogenesis. Recent contradictory findings indicated that TNF-α can also activate osteoblastogenesis. The paradoxical role of TNF-α in bone homeostasis seems to depend on the concentration and the differentiation state of the cell type used as well as on the exposure time. This review aims to summarize the recent contradictory findings on the regulation of bone homeostasis by TNF-α at the isolated cell, whole bone, and whole body levels. In addition, the involvement of TNF-α in the bone remodeling imbalance is observed in inflammatory joint diseases including rheumatoid arthritis and ankylosing spondylitis, which are associated with bone destruction and ectopic calcified matrix formation, respectively. Both diseases are associated with systemic/vertebral osteoporosis.Frontiers in Immunology 01/2014; 5:48.