Tanshinone IIA Regulates Osteoblast Differentiation and Promotes Fracture Healing via Mammalian Target of Rapamycin Complex 1 Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1737-1743
Author(s):  
Ming Fang ◽  
Xingwu Wang ◽  
Yongli Wei ◽  
Wuliang Yu ◽  
Jianmeng Lu
Keyword(s):  
Fracture Healing ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Callus Formation ◽  
Mammalian Target Of Rapamycin ◽  
Tanshinone Iia ◽  
Control Group ◽  
Osteoblast Proliferation ◽  
Mice Model ◽  
Mtorc1 Signaling

This study assessed the effect and potential molecular mechanism of tanshinone IIA on fracture healing. Mice model with fracture were established. Digital radiographic photographic system was used to detect callus formation after treatment with tanshinone II A (Tan IIA) and alkaline phosphatase (ALP) staining analyzed ALP activity. Osteoblast proliferation was also measured. Western blot and Quantitative real-time PCR (qRT-PCR) measured osteogenic markers expression. Compared with control group, Tan IIA treatment could increase callus formation, stimulate osteoblast proliferation, osteogenic proteins and genes expression, and activate mTORC1 signaling pathway. However, Tan IIA’s effects were significantly inhibited after rapamycin treatment. Tan IIA regulates osteoblast differentiation by mTORC1 signaling and promotes intramembranous ossification in the process of callus formation, which accelerates bone healing.

scholarly journals Electroacupuncture Reduces Weight in Diet-Induced Obese Rats via Hypothalamic Tsc1 Promoter Demethylation and Inhibition of the Activity of mTORC1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jincheng Leng ◽  
Feng Xiong ◽  
Junpeng Yao ◽  
Xiahuan Dai ◽  
Yulei Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Body Fat ◽  
Mammalian Target Of Rapamycin ◽  
Gene Promoter ◽  
Chow Group ◽  
Diet Group ◽  
The Body ◽  
Sprague Dawley ◽  
Tsc1 Gene ◽  
Mtorc1 Signaling

Subject. The study aimed to investigate the mechanism of electroacupuncture reducing weight via tuberous sclerosis complex 1 (Tsc1) promoter methylation, inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. Materials and Methods. Male Sprague-Dawley rats were divided into chow-fed group (chow group) or high-fat diet group (HF group) for 14 weeks. The obesity rats in HF group were randomly divided into electroacupuncture group (EA group) and diet-induced obesity (DIO) group, which received EA stimulation on bilateral ST25, RN12, SP6, and ST36 for 4 weeks or no further treatment, respectively. Methylation of the Tsc1 gene promoter and expression of agouti-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (PoMC) were detected at the 18th week. Results. At week 18, weight, body fat, and the body fat rate in DIO group were significantly higher than those of the chow and EA group. Compared with the chow group, the DIO group had increased methylation of the Tsc1 gene promoter and expression of mTORC1, AgRP, and NPY gene and decreased PoMC in the hypothalamus; after EA, methylation of the Tsc1 gene promoter, mRNA, and protein of the mTORC1 and expression of AgRP and NPY gene decreased and PoMC increased significantly. Conclusions. Our study could shed light on the potential pathway where EA exerts effects on the mechanism of EA treatment for obesity through the hypothalamic Tsc1 promoter demethylation and inhibition of the activity of mTORC1 signaling pathway.

The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway

2020 ◽  
Vol 156 ◽  
pp. 104798 ◽  
Author(s):  
Ahmad Tamaddoni ◽  
Elahe Mohammadi ◽  
Fatemeh Sedaghat ◽  
Durdi Qujeq ◽  
Atefeh As’Habi
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Anticancer Effects ◽  
Mtorc1 Signaling

scholarly journals Low concentration of rutin treatment might alleviate the cardiotoxicity effect of pirarubicin on cardiomyocytes via activation of PI3K/AKT/mTOR signaling pathway

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Junjie Fei ◽  
Yi Sun ◽  
Yuyin Duan ◽  
Jianming Xia ◽  
Songhua Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cultured Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Mammalian Target Of Rapamycin ◽  
Protective Role ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Mice Model ◽  
Low Concentration ◽  
Antioxidative Stress

Abstract Cancer is the leading cause of deaths around the world, especially in low- and middle- income countries. Pirarubicin (THP) is an effective drug for treatment of cancer, however, there still exists cardiotoxic effects of THP. Rutin is a kind of antioxidative compound extracted from plants, and might be a protective compound for cardiomyocytes. Phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critical for cellular survival, proliferation and metabolism, and thus we speculated rutin might perform a protective role in cardiomyocytes via PI3K/AKT/mTOR signaling pathway. And in this experiment, we first established a cardiotoxicity model of THP in mice model and cell models, and then found that rutin treatment could increase the proliferation of cells at low concentration. Then we explored the possible mechanism of the protective effect of rutin using Western blotting, quantitative polymerase chain reaction (qPCR) and ELISA methods, and found that the activation of PI3K/AKT/mTOR/nuclear factor-κB (NF-κB) signaling pathway was increased, and expression of downstream molecules involved in antioxidative stress were also increased. We further noticed that concentration of angiogenesis promoting factors were also increased in medium of cultured cells. Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of antioxidative stress enzymes with the increasing concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function.

scholarly journals Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

2021 ◽  
Vol 10 (19) ◽  
pp. 4362
Author(s):  
Ronald Peek ◽  
Lotte L. Eijkenboom ◽  
Didi D. M. Braat ◽  
Catharina C. M. Beerendonk
Keyword(s):  
Signaling Pathway ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Autologous Transplantation ◽  
Mammalian Target Of Rapamycin ◽  
Short Term ◽  
Ovarian Cortex ◽  
Short Term Exposure ◽  
Mtorc1 Signaling ◽  
Restoration Of Fertility

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

scholarly journals Role of BDNF-mTORC1 Signaling Pathway in Female Depression

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xianquan An ◽  
Xiaoxiao Yao ◽  
Bingjin Li ◽  
Wei Yang ◽  
Ranji Cui ◽  
...  
Keyword(s):  
Public Health ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Public Health Problem ◽  
Low Mood ◽  
Mtorc1 Signaling ◽  
Prevention And Treatment ◽  
Close Relationship ◽  
The Brain

Depression is a common psychological and mental disorder, characterized by low mood, slow thinking and low will, and even suicidal tendencies in severe cases. It imposes a huge mental and economic burden on patients and their families, and its prevention and treatment have become an urgent public health problem. It is worth noting that there is a significant gender difference in the incidence of depression. Studies have shown that females are far more likely to suffer from depression than males, confirming a close relationship between estrogen and the onset of depression. Moreover, recent studies suggest that the brain-derived neurotrophic factor- (BDNF-) mammalian target of rapamycin complex-1 (mTORC1) signaling pathway is a crucial target pathway for improving depression and mediates the rapid antidepressant-like effects of various antidepressants. However, it is not clear whether the BDNF-mTORC1 signaling pathway mediates the regulation of female depression and how to regulate female depression. Hence, we focused on the modulation of estrogen-BDNF-mTORC1 signaling in depression and its possible mechanisms in recent years.

scholarly journals The Effects of Autologous Platelet-Rich Plasma on the Bone Fracture Healing in Rabbits

2019 ◽  
Vol 12 (2) ◽  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Platelet Rich Plasma ◽  
Histological Finding ◽  
Control Group ◽  
Post Operation ◽  
Group A ◽  
Autologous Platelet Rich Plasma ◽  
Group B ◽  
Autologous Platelet

The purpose of this study was to evaluate the effects of an autologous platelet rich-plasma on femoral fracture healing in experimentally induced rabbits’ model. In this study, 34 local breed rabbits, around 2-2.5 kg body weight, were divided into two equal groups randomly; Group A: platelet-rich plasma (PRP) and Groups B: Control group. Rabbits in both groups underwent a complete mid-shaft transverse osteotomy of the femur by a fine electrical saw. After fracture induction, the rabbits in group A (PRP group) were treated by application of 0.5 ml of autologous PRP at the site of the fractured bone, while in group B (control), rabbits were injected with distilled water. Samples from the fractured femur were collected at 10th, 20th, 30th days post operation for radiological evaluation and at 10th, 14th, 20th, and 30th days for histopathological evaluation. In radiological study, it was found that the rate of callus formation in rabbits treated with PRP (Group A) were faster than the control group (Group B) at different periods. Similarly, in histological finding it found that the stages of healing were faster in Group A when compared with Group B. It was concluded that using autologous PRP has beneficial effect to enhance the process of bone healing in the rabbit’s model.

scholarly journals Boeravinone B promotes fracture healing in ovariectomyinduced osteoporotic rats via the regulation of NF-κB p65/IκB-α/SIRT-1 signaling pathway

2021 ◽  
Vol 18 (5) ◽  
pp. 955-960
Author(s):  
Jianlin Zhang ◽  
Longze Zong ◽  
Dongyu Bai
Keyword(s):  
Fracture Healing ◽  
Signaling Pathway ◽  
Normal Control ◽  
Bone Mineral ◽  
Normal Control Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α

Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats. Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IкB-α and SIRT1 proteins. Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-α and IL-1β significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05). Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway.

scholarly journals Flunixin Meglumine Enhanced Bone Fracture Healing in  Rabbits Associated with Activation of Early Collagen Deposition and Enhancement of Vascular Endothelial Growth Factor Expression

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2834
Author(s):  
Mohamed Elgendy ◽  
Gamal Elsayad ◽  
Magdi Seleim ◽  
Walied Abdo ◽  
Roua S. Baty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Bone Healing ◽  
Callus Formation ◽  
Control Group ◽  
Vascular Endothelial ◽  
Collagen Deposition ◽  
Flunixin Meglumine ◽  
Endothelial Growth Factor

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used postoperative analgesics, antipyretics, and anti-inflammatories, and they help prevent blood clotting. However, most NSAIDs delay bone healing. This study was aimed to investigate bone healing in a rabbit animal model by assessing the ability of flunixin meglumine (FM) and ketoprofen to induce fracture healing by examining histology, radiological changes, and vascular endothelial growth factor (VEGF) immunostaining during bone healing. For this purpose, 24 New Zealand rabbits were assigned to three groups: the control group, the FM group, and the ketoprofen group. Our results revealed that there were no intraoperative complications, and all surviving rabbits achieved full-weight bearing. Significant periosteal reaction and callus formation were confirmed at 2 postoperative weeks. Interestingly, FM enhanced callus formation, bone union, and remodeling in the FM group compared to the control and ketoprofen groups. FM enhanced bone healing through early collagen deposition and marked angiogenesis process activation by increasing the expression of VEGF. Our findings demonstrated, for the first time, the potential imperative action of FM in the bone healing process rather than other NSAIDs in animals.

scholarly journals Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE−/−Mice Fed with a High-Fat Diet

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhang ◽  
Pan Ren ◽  
Qunfu Kang ◽  
Weihong Liu ◽  
Sinai Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Blood Lipids ◽  
Mice Model ◽  
High Fat ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Plaque Area ◽  
Mtorc1 Signaling

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE−/−mice were randomized (n=10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c, IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/−mice as compared to the untreated mice (P<0.05,P<0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P<0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process.

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