Pharmacological activation of SIRT1 by metformin prevented trauma-induced heterotopic ossification through inhibiting macrophage mediated inflammation

Sun, Ziyang; Li, Juehong; Luo, Gang; Liu, Weixuan; He, Yunwei; Wang, Feiyan; Qian, Yun; Fan, Cunyi

doi:10.1016/j.ejphar.2021.174386

Cited by 17 publications

(16 citation statements)

References 35 publications

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“…Histologically, trauma-induced HO develops through endochondral ossification involving 4 stages: inflammation, chondrogenesis, osteogenesis, and maturation 23,24 . In previous studies, we found that reducing the early inflammatory response can significantly reduce HO formation 25,26 , indicating that the inflammatory response acts as a necessary starting factor for HO development. Furthermore, in human studies of combat-related trauma, several inflammatory cytokines (including IL-12p70, IL-6, and MCP-1) were demonstrated to be elevated in serum and drainage fluid and were suggested to be capable of independently predicting HO formation, indicating the importance of early inflammation in HO formation from a clinical perspective 27,28 .…”

Section: Discussionmentioning

confidence: 85%

Association Between Tranexamic Acid Use and Heterotopic Ossification Prevalence After Elbow Trauma Surgery

Liu¹,

Li²,

et al. 2023

Journal of Bone and Joint Surgery

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Background: Heterotopic ossification (HO) is a common complication of elbow trauma that can affect limb mobility.Inflammation is an initiating factor for HO formation. Tranexamic acid (TXA) can reduce the inflammatory response after orthopaedic surgery. However, evidence regarding the effectiveness of TXA use for HO prevention after elbow trauma surgery is lacking.Methods: This retrospective observational propensity-score-matched (PSM) cohort study was conducted from July 1, 2019, to June 30, 2021, at the National Orthopedics Clinical Medical Center, Shanghai, People's Republic of China. A total of 640 patients who underwent surgery following elbow trauma were evaluated. The present study excluded patients with an age of <18 years; those with a history of elbow fracture; those with a central nervous system injury, spinal cord injury, burn injury, or destructive injury; and those who had been lost to follow-up. After 1:1 matching on the basis of sex, age, dominant arm, injury type, open injury, comminuted fracture, ipsilateral trauma, time from injury to surgery, and nonsteroidal anti-inflammatory drug use, the TXA group and the no-TXA group comprised 241 patients each.Results: In the PSM population, the prevalence of HO was 8.71% in the TXA group and 16.18% in the no-TXA group (with rates of 2.07% and 5.80% for clinically important HO, respectively). Logistic regression analyses showed that TXA use was associated with a lower rate of HO (odds ratio [OR], 0.49; 95% CI, 0.28 to 0.86; p = 0.014) than no TXA use, as well as with a lower rate of clinically important HO (OR, 0.34; 95% CI, 0.11 to 0.91; p = 0.044). None of the baseline covariates significantly affected the relationship between TXA use and HO rate (p > 0.05 for all). Sensitivity analyses supported these findings.Conclusions: TXA prophylaxis may be an appropriate method for the prevention of HO following elbow trauma.

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Section: Discussionmentioning

confidence: 85%

Association Between Tranexamic Acid Use and Heterotopic Ossification Prevalence After Elbow Trauma Surgery

Liu¹,

Li²,

et al. 2023

Journal of Bone and Joint Surgery

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“…Our results showed that cell migration and tube formation decreased in the Sal B+EX527 and LY294002-treated macrophage cell culture supernatant groups. Previous studies found that EX527 increased NF- κ B p65 acetylation through the inhibition of SIRT, leading to the macrophage inflammatory responses [ 51 ]. Moreover, EX527 administration abolished the M2 phenotype polarization through inhibition of autophagy [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Limb Ischemia in Mice via Promoting SIRT1/PI3K/AKT Pathway-Mediated M2 Macrophage Polarization

Niu¹,

Cao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Salvianolic acid B (Sal B) is an effective treatment agent for ischemic disease in China. However, Sal B’s effects on peripheral arterial disease (PAD) and its mechanism remains poorly understood. Macrophage polarization plays a crucial role in PAD. Nevertheless, treatment modalities that increase the population of anti-inflammatory (M2) macrophages are limited. This study aimed to explore the protective effects of Sal B on limb perfusion and investigate the mechanism of Sal B-induced macrophage polarization. C57BL/6 male mice (6 weeks) were randomized into control, Model + NS, and Model + Sal B groups (n = 5). Then, we established a hind limb ischemia mouse model to assess the Sal B’s role (15 mg/kg/d) in PAD. We quantified the blood perfusion via laser speckle contrast imaging (LSCI) and measured the capillary density and muscle edema with CD31 and H&E staining. The Sal B-induced macrophage polarization was confirmed by qPCR and ELISA. The results showed that the Sal B group exhibited a significant improvement in the blood perfusion, capillary density, muscle edema, and M2 markers gene expressions. Cell migration and tube formation were promoted in the endothelial cells stimulated with a culture supernatant from Sal B-treated macrophages. In contrast, endothelial functions improved by Sal B-treated macrophages were impaired in groups treated with SIRT1 and PI3K inhibitors. These findings provide evidence for Sal B’s protective role in PAD and demonstrate the enhancement of macrophage polarization via the SIRT1/PI3K/AKT pathway.

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“…RAW cells (RAW 264.7), a rat macrophage cell line, were used for inflammation analysis in the present study. In accordance with previous studies [12,28], cells were pretreated with complete culture medium [Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin, 10 ng/mL macrophage colony-stimulating factor, and 100 ng/ mL lipopolysaccharide] for 24 hours to allow attachment. Subsequently, cells were treated with saline (control group), 1 μM dexamethasone (GC group), or 1 μM dexamethasone and 10 11 pellets/mL ASC-Exos (GC+ASC-Exo group) and further evaluated.…”

Section: Inflammation Analysismentioning

confidence: 99%

Anti-inflammatory and Tendon-Protective Effects of Adipose Stem Cell-Derived Exosomes with Concomitant Use of Glucocorticoids

Zhang

Han

et al. 2022

Stem Cells International

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Glucocorticoid (GC) injections are commonly used in clinical practice to relieve pain and improve function in patients with multiple shoulder disabilities but cause detrimental effects on rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. However, it is unclear whether additional treatment with ASC-Exos overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects. Thus, we aimed to investigate the anti-inflammatory effect of ASC-Exos with GCs and protective effect of ASC-Exos against GC-induced detriments. The present study comprised in vitro and in vivo studies. In vitro inflammatory analysis revealed that ASC-Exos exerted a synergic anti-inflammatory effect with GCs by significantly decreasing secretion of proinflammatory cytokines by RAW cells and increasing secretion of anti-inflammatory cytokines. In vitro cytoprotective analysis showed that ASC-Exos overrode GC-induced detrimental effects on tenocytes by significantly improving GC-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules and degradative enzyme inhibitors and significantly decreasing GC-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In vivo studies revealed that additional ASC-Exo injection restored impairments in histological and biomechanical properties owing to GC administration. Collectively, these results suggest that ASC-Exos exert a stronger anti-inflammatory effect in combination with GCs, overriding their detrimental effects on rotator cuff tendons.

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Pharmacological activation of SIRT1 by metformin prevented trauma-induced heterotopic ossification through inhibiting macrophage mediated inflammation

Cited by 17 publications

References 35 publications

Association Between Tranexamic Acid Use and Heterotopic Ossification Prevalence After Elbow Trauma Surgery

Association Between Tranexamic Acid Use and Heterotopic Ossification Prevalence After Elbow Trauma Surgery

Salvianolic Acid B Alleviates Limb Ischemia in Mice via Promoting SIRT1/PI3K/AKT Pathway-Mediated M2 Macrophage Polarization

Anti-inflammatory and Tendon-Protective Effects of Adipose Stem Cell-Derived Exosomes with Concomitant Use of Glucocorticoids

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