scholarly journals Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Qian Zhang ◽  
Bin Chen ◽  
Fuhua Yan ◽  
Jianbin Guo ◽  
Xiaofeng Zhu ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Interleukin 10 ◽  
Current Therapies ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Reduce Bone Loss

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

scholarly journals Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2621-2635 ◽  
Author(s):  
Seong Hee Ahn ◽  
Sook-Young Park ◽  
Ji-Eun Baek ◽  
Su-Youn Lee ◽  
Wook-Young Baek ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Free Fatty Acid Receptor

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4−/−) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4−/− and fat-1Tg+ mice over two generations to generate four genotypes of mice littermates: Ffar4+/+;fat-1Tg−, Ffar4+/+;fat-1Tg+, Ffar4−/−;fat-1Tg−, and Ffar4−/−;fat-1Tg+. Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1Tg+ mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In a high-fat diet-fed model, male fat-1Tg+ mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

scholarly journals The Role of Macrophage in the Pathogenesis of Osteoporosis

2019 ◽  
Vol 20 (9) ◽  
pp. 2093 ◽  
Author(s):  
Deng-Ho Yang ◽  
Meng-Yin Yang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Proinflammatory Cytokines ◽  
Bone Repair ◽  
Systemic Disease ◽  
Activated Macrophages

Osteoporosis is a systemic disease with progressive bone loss. The bone loss is associated with an imbalance between bone resorption via osteoclasts and bone formation via osteoblasts. Other cells including T cells, B cells, macrophages, and osteocytes are also involved in the pathogenesis of osteoporosis. Different cytokines from activated macrophages can regulate or stimulate the development of osteoclastogenesis-associated bone loss. The fusion of macrophages can form multinucleated osteoclasts and, thus, cause bone resorption via the expression of IL-4 and IL-13. Different cytokines, endocrines, and chemokines are also expressed that may affect the presentation of macrophages in osteoporosis. Macrophages have an effect on bone formation during fracture-associated bone repair. However, activated macrophages may secrete proinflammatory cytokines that induce bone loss by osteoclastogenesis, and are associated with the activation of bone resorption. Targeting activated macrophages at an appropriate stage may help inhibit or slow the progression of bone loss in patients with osteoporosis.

scholarly journals The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

2020 ◽  
Vol 9 (4) ◽  
pp. 184-198 ◽  
Author(s):  
Emily H. Steen ◽  
Xinyi Wang ◽  
Swathi Balaji ◽  
Manish J. Butte ◽  
Paul L. Bollyky ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Interleukin 10 ◽  
Tissue Fibrosis ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

scholarly journals The Prognostic Determinant of Interleukin-10 in Patients with Acute Ischemic Stroke: An Analysis from the Perspective of Disease Management

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen Sun ◽  
Shuhui Wang ◽  
Shanji Nan
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Clinical Severity ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Background. In patients with ischemic stroke, the role of anti-inflammatory cytokine Interleukin-10 (IL-10) in predicting risk and outcomes is not very clear. This study is aimed at prospectively assessing the prognostic determinant value of IL-10 in patients with acute ischemic stroke in a cohort of Chinese people. Methods. In a prospective cohort study, consecutive first-ever patients with acute ischemic stroke admitted to our hospital were included from October 2019 to October 2020. The serum level of IL-10 was measured at baseline. A structured follow-up telephone interview was performed on day 90 after admission. Logistic regression analyses were used to assess the prognostic value of IL-10 to predict the poor functional outcome (defined as a modified Rankin Scale score of 3 to 6) and mortality. Results. The median age of the 236 enrolled patients was 65 years (interquartile range (IQR), 56-76), and 57.6% were male. There was a negative correlation between the National Institutes of Health Stroke Scale (NIHSS) score and IL-10 serum levels ( r   Spearman = − 0.221 , P = 0.001 ). Patients with elevated IL-10 levels (> the highest quartile = 5.24   pg / mL ; n = 79 ) were at significantly lower risk of poor functional outcomes (odds ratio (OR), 0.35; 95% confidence interval (CI), 0.19 to 0.63; P < 0.001 ) and mortality ( OR = 0.24 ; 95% CI = 0.11 –0.52; P < 0.001 ) compared with patients with IL-10 levels in the lowest three quartiles. Conclusions. Reduced serum levels of IL-10 were independently associated with both the clinical severity at admission and a poor functional prognosis in ischemic stroke patients, suggesting that the anti-inflammatory cytokine IL-10 was an important prognostic determinant.

Abstract 43: Renal Hemodynamic and Excretory Responses to Systemic Administration of Interleukin-10 in Anesthetized Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Alexander Castillo ◽  
Dewan S Majid
Keyword(s):  
Receptor Antagonist ◽  
Inflammatory Cytokine ◽  
Interleukin 10 ◽  
Renal Tissue ◽  
Excretory Function ◽  
Anti Inflammatory ◽  
Renal Vascular ◽  
Renal Responses ◽  
Anti Inflammatory Cytokine

Recent studies have demonstrated that the anti-inflammatory cytokine, interleukin-10 (IL-10) is normally present in plasma and its protein is constitutively expressed in the renal tissue. However, the possible role of IL-10 in the regulation of renal hemodynamics and excretory function is not yet clearly defined. In the present study, we have examined the systemic and renal responses to intravenous administration of incremental doses of recombinant mouse IL-10 (0.015, 0.075 and 0.15 ng/min/g ; 45 min in each dose) in anesthetized mice (n=5). To determine the specificity of IL-10 actions, the responses to the middle dose were also assessed in the presence of its receptor antagonist, (mouse IL-10 Rα antibody; 1.5 ng/min/g; R&D system) in a separate group of mice (n=6). Standard clearance techniques were used to assess renal responses to infusions of IL-10 and its receptor antagonist. Renal blood flow (RBF) was determined by PAH clearances and glomerular filtration rate (GFR) was determined by inulin clearance. Infusion of IL-10 doses resulted in significant decreases in systemic mean arterial pressure (MAP; 98±1.9 to 89±3.9, 88±2.6 and 84±3.3 mmHg) and renal vascular resistance (RVR, 13.5±1.1 to 9.1±0.6, 7.1±0.5 and 7.1±0.5 mmHg/mL/min/g), increases in RBF (7.4±0.5 to 9.7±0.6, 10.6±0.5 and 9.8±0.6 mL/min/g) and GFR (1.06±0.05 to 1.45±0.13, 1.51±0.13 and 1.53±0.28 mL/min/g) without significant changes in urine flow (6.6±0.5 to 5.3±0.5, 5.5±1.1 and 5.3±1.1 μL/min/g ) or sodium excretion (0.58±0.08 to 0.52±0.18, 0.57±0.19 and 0.69±0.26 μmol/min/g). Administration of IL-10 receptor antagonist alone did not cause significant changes in MAP (90±3.7 to 89±5.3 mmHg), RVR (11.5±1.9 to 11.6±3.0 mmHg/mL/min/g), RBF (8.8±1.3 to 10.4±2.5 mL/min/g), GFR (1.06±0.08 to 1.20±0.19 mL/min/g) or other renal parameters. Infusion of the middle dose of IL-10 in the receptor antagonist pretreated mice failed to cause significant changes in RBF or GFR or other parameters confirming the specificity of its receptor activity in the mediation of observed renal responses to IL-10 infusion. These data suggest that the anti-inflammatory cytokine, IL-10 exerts vasodilator and hyper-filtration effects in the kidney but minimally influences the renal excretory function.

scholarly journals ASSOCIATION BETWEEN PERIODONTAL DISEASE AND OSTEOPOROSIS

2017 ◽  
Vol 26 (3) ◽  
pp. 107-114
Author(s):  
Dan Piperea-Sianu ◽  
◽  
Adela M. Ceau ◽  
Mara Carsote ◽  
Alexandru G. Croitoru ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Periodontal Disease ◽  
Alveolar Bone ◽  
Serum Levels ◽  
Bone Lysis ◽  
Local Impact ◽  
Systemic Bone Loss

Osteoporosis and periodontal disease (PD) are two chronic diseases, characterized by bone loss, with systemic or local impact (alveolar bone). Both pathologies have a progressive evolution, leading to systemic bone loss in the case of osteoporosis and bone lysis localized in the alveolar bone in the case of periodontal disease. The present paper presents recent data from the literature on the association between periodontal disease and osteoporosis, on the role of cytokines in the bone resorption-apposition imbalance, and on how periodontal disease causes changes in serum levels of cytokines, leading to disorders in the systemic bone formation. We also found it useful, especially for rheumatologists, to outline the extent to which periodontal disease can create a systemic context favorable to the development of osteoporosis.

Changes in bone metabolism associated with exposure to industrial vibration

2020 ◽  
pp. 766-766
Author(s):  
A. V. Sukhova ◽  
E. N. Kryuchkova
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Metabolism ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Local Vibration ◽  
Markers Of Bone Formation

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.

scholarly journals Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 199
Author(s):  
Urara Tanaka ◽  
Shunichi Kajioka ◽  
Livia S. Finoti ◽  
Daniela B. Palioto ◽  
Denis F. Kinane ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Resorption ◽  
Bone Loss ◽  
Inflammatory Cytokines ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Osteoblastic Cell Line ◽  
Anti Inflammatory

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Model ◽  
Interleukin 10 ◽  
Immune Functions ◽  
Murine Lupus ◽  
Anti Inflammatory ◽  
In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

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