Dataset Information

Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells.

ABSTRACT:

Objectives

Periodontitis is one of the most widespread inflammatory diseases; it causes tooth loss and is also associated with a variety of systemic diseases. Mesenchymal stem cells (MSCs) have been used to treat periodontitis. However, it is unknown whether bacterial toxins in the periodontal environment affect MSC-mediated periodontal regeneration. Porphyromonas gingivalis lipopolysaccharides (Pg-LPS) are key toxins for development of periodontitis. The purpose of the present study was to investigate effects of P. gingivalis LPS on biological properties of MSCs.

Materials and methods

Mesenchymal stem cells from bone marrow (BMMSCs) were treated with different concentrations of P. gingivalis LPS (0.1-10 ?g/ml), then its effects were evaluated on biological properties of BMMSCs including proliferation, apoptosis, osteogenic differentiation and capacities to inhibit activated T cells.

Results

Low concentration of P. gingivalis LPS (0.1 ?g/ml) accelerated MSC proliferation, osteogenic differentiation and capacities to inhibit activated T cells via up-regulation of nitric oxide. However, high concentration of P. gingivalis LPS (10 ?g/ml) reduced MSC proliferation, osteogenic differentiation and capacities to inhibit activated T cells.

Conclusions

Mesenchymal stem cells were functionally different following exposure to P. gingivalis LPS at the investigated concentrations. These findings suggest that MSC-mediated periodontal regeneration may be regulated by P. gingivalis LPS.

SUBMITTER: Tang J

PROVIDER: S-EPMC6496502 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells.

Tang J J Wu T T Xiong J J Su Y Y Zhang C C Wang S S Tang Z Z Liu Y Y

Cell proliferation 20150210 2

<h4>Objectives</h4>Periodontitis is one of the most widespread inflammatory diseases; it causes tooth loss and is also associated with a variety of systemic diseases. Mesenchymal stem cells (MSCs) have been used to treat periodontitis. However, it is unknown whether bacterial toxins in the periodontal environment affect MSC-mediated periodontal regeneration. Porphyromonas gingivalis lipopolysaccharides (Pg-LPS) are key toxins for development of periodontitis. The purpose of the present study was ...[more]

PMID: 25676907

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Project description:BackgroundPeriodontal tissue regeneration is the ultimate goal of periodontitis treatment. Exosomes are nanoscale vesicles secreted by cells that participate in and regulate the physiological activities between cells. However, the relationship between inflammatory macrophage-derived exosomes and osteoblast differentiation in periodontitis has not been thoroughly reported. Here, we attempt to explore the role of inflammatory macrophage-derived exosomes in crosstalk with osteoblasts.MethodsPorphyromonas gingivalis lipopolysaccharide was used to stimulate macrophages and inflate their inflammatory cellular state. Exosomes were extracted from inflammatory macrophages using supercentrifugation, and their characteristics were detected by transmission electron microscopy, particle size analysis, and Western blotting. Exosome uptake bybone marrow mesenchymal stem cells (BMSCs) was observed by fluorescence microscopy. The effects of exosomes on the BMSC inflammatory response and on osteogenic differentiation were detected by quantitative polymerase chain reaction and Western blot analysis. Alkaline phosphatase activity was tested for verification.ResultsWe successfully extracted and identified inflammatory macrophage-derived exosomes and observed that BMSCs successfully took up exosomes. Inflammatory macrophage-derived exosomes upregulated the expression levels of the inflammatory factors interleukin-6 and tumour necrosis factor-alpha in BMSCs and mediated inflammatory stimulation. Additionally, they inhibited the transcription levels of the osteogenic genes alkaline phosphatase, type I collagen, and Runt-related transcription factor 2 as well as the alkaline phosphatase activity, while the use of the exosome inhibitor GW4869 attenuated this effect.ConclusionOur study shows that macrophages in periodontitis can mediate inflammatory stimulation and inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells through the exosome pathway. Interference with exosome secretion is likely to be a promising method for bone tissue regeneration in inflammatory states.

Project description:IntroductionSecondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice.MethodsThe effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice.ResultsSystemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts.ConclusionsThese findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus.

Dataset Information

Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells.

Objectives

Materials and methods

Results

Conclusions

Publications

Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells.

Similar Datasets

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