IL-6, IL-1β, and TNF-α only in combination influence the osteoporotic phenotype in Crohn’s patients via bone formation and bone resorption

Blaschke, Martina; Koepp, Regine; Cortis, Julia; Komrakova, Marina; Schieker, Matthias; Hempel, Ute; Siggelkow, Heide

doi:10.17219/acem/67561

Cited by 47 publications

(40 citation statements)

References 37 publications

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“…Together, these results suggest that low‐grade inflammation promotes or is associated with bone loss in some postmenopausal women. Consistent with these findings, men and women with chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease, and some viral (ie, human immunodeficiency virus [HIV]) infections develop osteoporosis . Despite these observations, questions as to the nature and the contribution of inflammation to postmenopausal osteoporosis have lingered.…”

Section: Introductionmentioning

confidence: 98%

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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The loss of estrogen (E2) initiates a rapid phase of bone loss leading to osteoporosis in one‐half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E2 activates low‐grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E2 regulates the abundance of dendritic cells (DCs) that express IL‐7 and IL‐15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E2, DCs become long‐lived, leading to increased IL‐7 and IL‐15. We find that IL‐7 and IL‐15 together, but not alone, induced antigen‐independent production of IL‐17A and TNFα in a subset of memory T cells (TMEM). OVX of mice with T‐cell–specific ablation of IL15RA showed no IL‐17A and TNFα expression, and no increase in bone resorption or bone loss, confirming the role of IL‐15 in activating the TMEM and the need for inflammation. Our results provide a new mechanism by which E2 regulates the immune system, and how menopause leads to osteoporosis. The low‐grade inflammation is likely to cause or contribute to other comorbidities observed postmenopause. © 2020 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 98%

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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“…2a-c). None of the single cytokines affected the SLC14A1 mRNA expression; however, when applied in combination (IL-6 10 pg/mL; TNF-alpha 5 pg/mL; and IL-1 beta 1 pg/mL [11]) the cytokines IL-6, TNF-alpha, and IL-1beta induced a significant reduction of SLC14A1 mRNA expression (▶Fig. 2d).…”

Section: Resultsmentioning

confidence: 98%

“…Therefore, identifying the gene(s) responsible for the "switch" from osteogenesis to adipogenesis is of great research interest, as these genes could represent potential targets for the development of anti-osteoporosis drugs. Furthermore, an interaction of cytokines between bone and fat cells has also been observed [10,11]. High levels of cytokines have been found in bone deprived of estrogens, [12][13][14] and this finding shows a positive association with histological bone resorption parameters and a negative association with bone formation parameters.…”

Section: Introductionmentioning

confidence: 82%

“…We also investigated whether externally applied cytokines have an effect on SLC14A1 mRNA expression by exposing cells to cytokines (IL-6, IL-1 beta, and TNF-alpha) [40] that are known to be associated with increased bone resorption in postmenopausal osteoporosis [14,26,41] or secondary osteoporosis (e. g., Crohn's disease) [11,42]. In a previous study, we showed that only in combination cytokines did affect bone markers, while cytokines applied singly did not possess any effect in hMSCs [11]. Similarly, in the present study, exogenous treatment with each cytokine singly did not affect SLC14A1 mRNA expression, whereas presenting the cytokines in combination decreased SLC14A1 expression, corresponding to the decreased expression in bone cell cultures derived from patients with metabolic bone disease detected in our study.…”

Section: Discussionmentioning

confidence: 99%

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Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Komrakova

Blaschke

Ponce

et al. 2020

Exp Clin Endocrinol Diabetes

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The human urea transporter SLC14A1 (HUT11/UT-B) has been suggested as a marker for the adipogenic differentiation of bone cells with a relevance for bone diseases. We investigated the function of SLC14A1 in different cells models from bone environment. SLC14A1 expression and cytokine production was investigated in bone cells obtained from patients with osteoporosis. Gene and protein expression of SLC14A1 was studied during adipogenic or osteogenic differentiation of human mesenchymal progenitor cells (hMSCs) and of the single-cell–derived hMSC line (SCP-1), as well as in osteoclasts and chondrocytes. Localization was determined by histochemical methods and functionality by urea transport experiments. Expression of SLC14A1 mRNA was lower in cells from patients with osteoporosis that produced high levels of cytokines. Accordingly, when adding a combination of cytokines to SCP-1 SLC14A1 mRNA expression decreased. SLC14A1 mRNA expression decreased after both osteogenic and more pronounced adipogenic stimulation of hMSCs and SCP-1 cells. The highest SLC14A1 expression was determined in undifferentiated cells, lowest in chondrocytes and osteoclasts. Downregulation of SLC14A1 by siRNA resulted in an increased expression of interleukin-6 and interleukin-1 beta as well as adipogenic markers. Urea influx through SLC14A1 increased expression of osteogenic markers, adipogenic markers were suppressed. SLC14A1 protein was localized in the cell membrane and the cytoplasm. Summarizing, the SLC14A1 urea transporter affects early differentiation of hMSCs by diminishing osteogenesis or by favoring adipogenesis, depending on its expression level. Therefore, SLC14A1 is not unequivocally an adipogenic marker in bone. Our findings suggest an involvement of SLC14A1 in bone metabolism and inflammatory processes and disease-dependent influences on its expression.

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“…The small change in IL-1b expression can lead to more changes in some ''downstream factor'' through a cascade reaction. 15 Increased IL-1b levels may upregulate the expression of bone remodeling factors. 13 Iwasaki et al found that increased IL-1b locally or systemically accelerates the rate of tooth movement, indicating that the IL-1b expression level is positively related to the local bone remodeling activity.…”

Section: Resultsmentioning

confidence: 99%

Comparative Study of 660 and 830 nm Photobiomodulation in Promoting Orthodontic Tooth Movement

Yang

2019

Photobiomodulation, Photomedicine, and Laser Surgery

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Objective: Photobiomodulation (PBM) can usefully promote wound healing and relieve pain via its biological effects, with a wide range of applications in clinical medicine. The aim of the present study was to investigate the effect of 660 and 830 nm PBM on orthodontic tooth movement. Background data: PBM is based on the biological effects of diode laser irradiation on tissues, promoting cell proliferation and activity. Materials and methods: An orthodontic force was applied to the upper right first molars exposed to a 660 and 830 nm PBM (LHH-500I; Beijing Long Hui Heng Medical Science and Technology Development Corporation) on days 0, 1, 2, 3, 4, 5, and 7 for 50 sec with power density of 0.1 W/cm 2 (a beam area of 0.5 cm 2 , radiate power of 0.05 W), energy density of 5 J/cm 2 within 14 days, and a control group with no laser irradiation. Tooth movement was analyzed using a stereomicroscope, the number of osteoclasts determined by tartrate-resistant acid phosphatase (TRAP), and the expression of bone remodeling factors evaluated by immunohistochemistry. Results: The expression of IL-1b, RANKL, and OPG was significantly stimulated in the 660 and 830 nm groups. The expression of RANKL was significantly higher in the 660 nm group than in the 830 nm group on days 5 and 7; however, there was no significant difference in the expression of OPG and IL-1b between the 660 and 830 nm groups on days 1, 2, 3, 4, 5, 7, and 14. On days 3 and 5, the number of osteoclasts in the 660 nm group was higher than that in the 830 nm group, and the difference was statistically significant. Tooth movement over 14 days was significantly higher in the 660 and 830 nm groups than in the control group, and there was no significant difference between the 660 and 830 nm groups finally. Conclusions: Both 660 and 830 nm can accelerate the orthodontic tooth movement and promote alveolar bone remodeling on the compression side. Although the difference of tooth movement over 14 days between the two groups was not statistically significant; however, 660 nm PBM to accelerate bone remodeling is stronger than 830 nm PBM at an early stage.

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IL-6, IL-1β, and TNF-α only in combination influence the osteoporotic phenotype in Crohn’s patients via bone formation and bone resorption

Cited by 47 publications

References 37 publications

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Comparative Study of 660 and 830 nm Photobiomodulation in Promoting Orthodontic Tooth Movement

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