scholarly journals Limonoid Triterpene, Obacunone Increases Runt-Related Transcription Factor 2 to Promote Osteoblast Differentiation and Function

2021 ◽  
Vol 22 (5) ◽  
pp. 2483
Author(s):  
Kyung-Ran Park ◽  
SooHyun Kim ◽  
MyoungLae Cho ◽  
Hyung-Mun Yun
Keyword(s):  
Transcription Factor ◽  
Osteoblast Differentiation ◽  
Bone Diseases ◽  
Nuclear Accumulation ◽  
Root Bark ◽  
Dependent Manner ◽  
Matrix Mineralization ◽  
Related Transcription Factor ◽  
Anti Inflammatory ◽  
Dose Dependent

Root bark of Dictamnus dasycarpus Turcz. has been widely used as a traditional medicine and is a well-known anti-inflammatory agent. We isolated limonoid triterpene, obacunone (Obac) from the dried root bark of D. dasycarpus. Obac has been reported to exhibit varieties of biological activities including anti-inflammatory, anti-cancer, and anti-oxidant effects. This study aimed to investigate the beneficial effects and biological mechanisms of Obac in osteoblast differentiation and bone matrix mineralization. In the present study, Obac at concentrations ranging from 1 to 100 μM showed no proliferation effects in MC3T3-E1. The treatment of Obac (1 and 10 μM) increased wound healing and migration rates in a dose-dependent manner. Alkaline phosphatase (ALP) staining and activity showed that Obac (1 and 10 μM) enhanced early osteoblast differentiation in a dose-dependent manner. Obac also increased late osteoblast differentiation in a dose-dependent manner, as indicated by the mineralized nodule formation of ARS staining. The effects of Obac on osteoblast differentiation was validated by the levels of mRNAs encoding the bone differentiation markers, including Alp, bone sialoprotein (Bsp), osteopontin (Opn), and osteocalcin (Ocn). Obac increased the expression of bone morphogenetic protein (BMP), and the phosphorylation of smad1/5/8, and the expression of runt-related transcription factor 2 (RUNX2); Obac also inhibited GSK3β and upregulated the protein level of β-catenin in a dose-dependent manner during osteoblast differentiation. Obac-mediated osteoblast differentiation was attenuated by a BMP2 inhibitor, Noggin and a Wnt/β-catenin inhibitor, Dickkopf-1 (Dkk1) with the abolishment of RUNX2 expression and nuclear accumulation by Obac. Taken together, the findings of this study demonstrate that Obac has pharmacological and biological activates to promote osteoblast differentiation and bone mineralization through BMP2, β-catenin, and RUNX2 pathways, and suggest that Obac might be a therapeutic effect for the treatment and prevention of bone diseases such as osteoporosis and periodontitis.

scholarly journals Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor

2020 ◽  
Vol 21 (24) ◽  
pp. 9579
Author(s):  
Kyung-Ran Park ◽  
SooHyun Kim ◽  
MyoungLae Cho ◽  
Sang Wook Kang ◽  
Hyung-Mun Yun
Keyword(s):  
Transcription Factor ◽  
Cell Migration ◽  
Protein Level ◽  
Osteoblast Differentiation ◽  
Signaling Molecules ◽  
Dependent Manner ◽  
Alizarin Red ◽  
Matrix Mineralization ◽  
Related Transcription Factor ◽  
Dose Dependent

Styrax Japonica Sieb. et Zucc. has been used as traditional medicine in inflammatory diseases, and isolated compounds have shown pharmacological activities. Pinoresinol glucoside (PIN) belonging to lignins was isolated from the stem bark of S. Japonica. This study aimed to investigate the biological function and mechanisms of PIN on cell migration, osteoblast differentiation, and matrix mineralization. Herein, we investigated the effects of PIN in MC3T3-E1 pre-osteoblasts, which are widely used for studying osteoblast behavior in in vitro cell systems. At concentrations ranging from 0.1 to 100 μM, PIN had no cell toxicity in pre-osteoblasts. Pre-osteoblasts induced osteoblast differentiation, and the treatment of PIN (10 and 30 μM) promoted the cell migration rate in a dose-dependent manner. At concentrations of 10 and 30 μM, PIN elevated early osteoblast differentiation in a dose-dependent manner, as indicated by increases in alkaline phosphatase (ALP) staining and activity. Subsequently, PIN also increased the formation of mineralized nodules in a dose-dependent manner, as indicated by alizarin red S (ARS) staining, demonstrating positive effects of PIN on late osteoblast differentiation. In addition, PIN induced the mRNA level of BMP2, ALP, and osteocalcin (OCN). PIN also upregulated the protein level of BMP2 and increased canonical BMP2 signaling molecules, the phosphorylation of Smad1/5/8, and the protein level of Runt-related transcription factor 2 (RUNX2). Furthermore, PIN activated non-canonical BMP2 signaling molecules, activated MAP kinases, and increased β-catenin signaling. The findings of this study indicate that PIN has biological roles in osteoblast differentiation and matrix mineralization, and suggest that PIN might have anabolic effects in bone diseases such as osteoporosis and periodontitis.

scholarly journals Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation

2020 ◽  
Vol 295 (33) ◽  
pp. 11669-11681 ◽  
Author(s):  
Jun Tang ◽  
Jing Xie ◽  
Wei Chen ◽  
Chenyi Tang ◽  
Jinjin Wu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Bone Diseases ◽  
Conditional Knockout ◽  
Bone Homeostasis ◽  
Exact Function ◽  
Related Transcription Factor ◽  
Transcription Factor 1 ◽  
Osteoblast Maturation

Despite years of research investigating osteoblast differentiation, the mechanisms by which transcription factors regulate osteoblast maturation, bone formation, and bone homeostasis is still unclear. It has been reported that runt-related transcription factor 1 (Runx1) is expressed in osteoblast progenitors, pre-osteoblasts, and mature osteoblasts; yet, surprisingly, the exact function of RUNX1 in osteoblast maturation and bone formation remains unknown. Here, we generated and characterized a pre-osteoblast and differentiating chondrocyte-specific Runx1 conditional knockout mouse model to study RUNX1's function in bone formation. Runx1 ablation in osteoblast precursors and differentiating chondrocytes via osterix-Cre (Osx-Cre) resulted in an osteoporotic phenotype and decreased bone density in the long bones and skulls of Runx1f/fOsx-Cre mice compared with Runx1f/f and Osx-Cre mice. RUNX1 deficiency reduced the expression of SRY-box transcription factor 9 (SOX9), Indian hedgehog signaling molecule (IHH), Patched (PTC), and cyclin D1 in the growth plate, and also reduced the expression of osteocalcin (OCN), OSX, activating transcription factor 4 (ATF4), and RUNX2 in osteoblasts. ChIP assays and promoter activity mapping revealed that RUNX1 directly associates with the Runx2 gene promoter and up-regulates Runx2 expression. Furthermore, the ChIP data also showed that RUNX1 associates with the Ocn promoter. In conclusion, RUNX1 up-regulates the expression of Runx2 and multiple bone-specific genes, and plays an indispensable role in bone formation and homeostasis in both trabecular and cortical bone. We propose that stimulating Runx1 activity may be useful in therapeutic approaches for managing some bone diseases such as osteoporosis.

Ziyuglycoside I Upregulates RUNX2 through ERK1/2 in Promoting Osteoblast Differentiation and Bone Mineralization

2021 ◽  
pp. 1-18
Author(s):  
Kyung-Ran Park ◽  
Joon Yeop Lee ◽  
MyoungLae Cho ◽  
Hyung-Mun Yun
Keyword(s):  
Cell Migration ◽  
Osteoblast Differentiation ◽  
Bone Mineralization ◽  
Biological Effects ◽  
Bone Diseases ◽  
Nuclear Accumulation ◽  
Herbaceous Plant ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Alizarin Red

Sanguisorba officinalis L. (Rosaceae) is a perennial herbaceous plant and its roots have been used as an important traditional medicine for over 2000 years. Ziyuglycoside I (Ziyu), an active compound isolated from the roots of S. officinalis L., has shown biological effects such as anti-oxidant, antiviral, and antiwrinkle activities. This study aimed to elucidate the underlying mechanisms of action of Ziyu on cytotoxicity, migration, and differentiation of pre-osteoblasts. Herein, at concentrations ranging from 1 to 100 [Formula: see text]M, Ziyu was not cytotoxic against pre-osteoblasts. Alkaline phosphatase activity assay and staining, and migration assay showed that Ziyu increased cell migration and promoted early osteoblast differentiation, followed by the enhancement of mineralized nodule formation in a dose-dependent manner, as indicated by Alizarin Red S staining. In addition, Ziyu increased the protein levels of runt-related transcription factor 2 (RUNX2) during osteoblast differentiation, whereas it did not affect the phosphorylation of Smad1/5/8 and GSK3b and expression of [Formula: see text]-catenin. Ziyu also activated ERK1/2 and mitogen-activated protein kinase during osteoblast differentiation, and ERK1/2 inhibitor attenuated Ziyu-mediated RUNX2 expression and nuclear accumulation. Furthermore, Ziyu-mediated early and late osteoblast differentiation was significantly suppressed by the inhibition of ERK1/2, which was accompanied by attenuation in the mRNA levels of osteoblast-related genes including bone sialoprotein, osteopontin, and osteocalcin. Taken together, the findings of this study provide evidence that Ziyu promotes cell migration, osteoblast differentiation, and bone mineralization and suggest a potential role for Ziyu in the treatment of bone diseases.

scholarly journals High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1981 ◽  
Author(s):  
Qiufen Mo ◽  
Aikun Fu ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Yang Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Systemic Inflammation ◽  
Body Weight Gain ◽  
High Dose ◽  
Dependent Manner ◽  
Glucose And Lipid Metabolism ◽  
Glycerol Monolaurate ◽  
Indigenous Microbiota ◽  
Anti Inflammatory ◽  
Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

scholarly journals Compound Traditional Chinese Medicine Dermatitis Ointment Ameliorates Inflammatory Responses and Dysregulation of Itch-Related Molecules in AD

2021 ◽  
Author(s):  
Rongrong Zhang ◽  
Shuai Shao ◽  
Yingxin Shen ◽  
Jiaming Sun ◽  
Songlan Piao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Inflammatory Responses ◽  
Dependent Manner ◽  
Inflammatory Skin Disease ◽  
Fingerprint Analysis ◽  
Hplc Fingerprint ◽  
Effective Components ◽  
Anti Inflammatory ◽  
Dose Dependent

Abstract Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by an itchy and scaly rash. Compound traditional Chinese medicine dermatitis ointment (CTCMDO) is a traditional classics aimed at AD composed of a mixture of extracts from five plants known to have anti-inflammatory and antiallergic effects. Materials and methods: In this study, we used HPLC and LC/MS to analyze the effective components of CTCMDO in detail and establish its HPLC fingerprint analysis. On this basis, this article studied the anti-inflammatory and antipruritic activities of CTCMDO in the treatment of DNCB-induced AD in mice.Results: Through comparison with literature data, a total of 43 compounds were identified, including phenylpropionic acid compounds; alkaloid compounds; curcumin compounds and lignans. On this basis, a fingerprint with 17 common peaks was established. In AD-like mice, CTCMDO treatment suppressed the scratching behavior induced by DNCB in a dose-dependent manner and inhibited the production of Th1/2 cytokines in serum. CTCMDO treatment reversed the up regulation of P substance levels of itch-related genes in the skin. Furthermore, CTCMDO suppressed the phosphorylation of JNK、ERK and p38 in the skin. Conclusion: In all, our work indicated that CTCMDO can signifificantly attenuate the pathological alterations of Th1/2 cytokines and itch-related mediators, and inhibit the phosphorylation of MAPKs to treat AD.

scholarly journals Evaluation of Analgesic and Anti-inflammatory Activities of Polyalthia simiarum (Hook. F. &Thomson)

2019 ◽  
Vol 5 (1) ◽  
pp. 18-23
Author(s):  
Selina Kabir ◽  
Ronok Zahan ◽  
Abdullah Mohammad Sarwaruddin Chowdhury ◽  
Choudhury Mahmood Hasan ◽  
Mohammad Abdur Rashid
Keyword(s):  
Acetic Acid ◽  
Analgesic Activity ◽  
Biological Activities ◽  
Dependent Manner ◽  
Paw Edema ◽  
Immersion Method ◽  
Ongoing Research ◽  
Tail Immersion ◽  
Anti Inflammatory ◽  
Dose Dependent

Background: Polyalthia simiarum (Hook. F. &Thomson) exhibits different effects in human body. Objective: As a part of ongoing research on medicinal plants of Bangladesh, the present study is focused to investigate the analgesic and anti-inflammatory activities of stem bark of Polyalthia simiarum (Annonaceae). Methodology: The ethyl acetate (EA) and petroleum ether (PE) extracts were subjected to qualitative chemical investigation for the identification of different phytoconstituents. The analgesic activity was determined for its central and peripheral pharmacological actions using tail immersion method and acetic acid-induced writhing test. The anti-inflammatory activity was evaluated by carrageenan induced paw edema in rats. Analgesic and anti-inflammatory data were evaluated statistically analysed by Dunnett’s-T test. Result: Both extracts at the dose of 50- and 100 mg/kg b.w., produced significant increase in pain threshold in tail immersion method whereas significantly reduced the writhing caused by acetic acid in a dose dependent manner. The EA and PE extracts showed anti-inflammatory activities at 50- and 100 mg/kg body weight. Among all the extracts, the EA extract showed a dose dependent and comparable analgesic activity in all the tested methods and also reduced the paw edema considerably (27.5% and 39.1% inhibition after 4h), in dose dependent manner when compared to carrageenan induced control rat. Conclusion: Therefore, the EA and PE extracts of Polyalthia simiarum were capable to exhibit moderate analgesic and anti-inflammatory activities. This is the first report of analgesic and anti-inflammatory potential of Polyalthia simiarum and can be further investigated to isolate the active compounds responsible for the biological activities. Journal of National Institute of Neurosciences Bangladesh, 2019;5(1): 18-23

scholarly journals Comparative Evaluation of Analgesic, Anti-inflammatory and Antipyretic Effects of Synthetic Derivatives of Organoantimony (?) Ferocenyl Benzoate with Piroxicam

2016 ◽  
Vol 19 (1) ◽  
pp. 15-24
Author(s):  
Muhammad Shoaib Akhtar ◽  
Zulfiqar Khan ◽  
Muhammad Naveed Mushtaq ◽  
Muhammad Salman Akhtar
Keyword(s):  
Pharmaceutical Journal ◽  
Significant Inhibition ◽  
Diffusion Method ◽  
Dependent Manner ◽  
Standard Drug ◽  
Compound A ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Synthetic Derivatives ◽  
Dose Dependent

The current study was planned to evaluate comparative anti-inflammatory, analgesic and anti-pyretic activities of two newly synthesized organo-antimony (v) ferrocenyl benzoate derivatives with piroxicam. Anti-microbial activity of these compounds was also screened against two microorganisms. Analgesic effect of test compounds was evaluated by formalin-induced paw licking test in mice. The test compounds at 50 and 100 mg/kg b.w. doses exhibited significant (p<0.001) reduction of paw licking in treated mice comparable with standard drug piroxicam. Anti-inflammatory activity was assessed against carrageenan-induced paw oedema. The compound A produced anti-inflammatory effects comparable with standard piroxicam in dose dependent manner whereas compound B showed better effects than piroxicam at dose of 100 mg/kg body weight. To investigate anti-pyretic activity, fever was induced by administration of Brewer’s yeast in mice. Compound A showed highly significant inhibition of pyrexia (p<0.001) comparable to piroxicam after 3 hours while compound B (50 and 100 mg/kg) produced relatively lower anti-pyretic effect than standard drug. Antibacterial activity determined by disc diffusion method showed that compound B was relatively more effective than compound A against Staphylococcus aureus and Klebsiella pneumoniae. It is conceivable that both the tested compounds possessed anti-inflammatory, analgesic, anti-pyretic and anti-microbial effects even after the structural modification of parent compound.Bangladesh Pharmaceutical Journal 19(1): 15-24, 2016

scholarly journals Anti-inflammatory Potential of Silk Sericin

2013 ◽  
Vol 8 (4) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Pornanong Aramwit ◽  
Pasarapa Towiwat ◽  
Teerapol Srichana
Keyword(s):  
Negative Control ◽  
Dependent Manner ◽  
Silk Sericin ◽  
Plantar Surface ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Right ◽  
Dose Dependent ◽  
Control Water

Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats’ paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats’ tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

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