scholarly journals DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4455
Author(s):  
Zhengmeng Yang ◽  
Lu Feng ◽  
Haixing Wang ◽  
Yucong Li ◽  
Jessica Hiu Tung Lo ◽  
...  
Keyword(s):  
Bone Formation ◽  
Functional Role ◽  
Bioactive Compound ◽  
Osteoporosis Treatment ◽  
Sesamum Indicum ◽  
Common Disease ◽  
Dependent Manner ◽  
Pharmaceutically Active Compounds ◽  
Compound Library ◽  
Dual Functional

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/β-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

A Cytotoxic Natural Product from Patrinia villosa Juss

2019 ◽  
Vol 19 (11) ◽  
pp. 1399-1404 ◽  
Author(s):  
Yangcheng Liu ◽  
Wei Liu ◽  
Changlan Chen ◽  
Zheng Xiang ◽  
Hongwei Liu
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Silica Gel ◽  
Column Chromatography ◽  
Bioactive Compound ◽  
Antitumor Agent ◽  
2D Nmr ◽  
Preparative Hplc ◽  
Dependent Manner ◽  
2D Nmr Spectra

Background and Purpose:: Patrinia villosa Juss is an important Chinese herbal medicine widely used for thousands of years, but few reports on the ingredients of the herb have been presented. In this study, we aim to isolate the bioactive compound from the plant. Material and Methods:: The air-dried leaves of P. villosa (15kg) were extracted three times with 70% EtOH under reflux. The condensed extract was suspended in H2O and partitioned with light petroleum, dichloromethane and n-BuOH. The dichloromethane portion was then subjected to normal-phase silica gel column chromatography, ODS silica gel column chromatography and semi-preparative HPLC to yield compound 1. Cytotoxicities of 1 were assayed on HepG2, A549 and A2780 cell lines. The mechanism of apoptosis and cell cycle on A549 was confirmed subsequently. Results: A new impecylone (Impecylone A) was isolated from the leaves of Patrinia villosa Juss, and its structures were established using 1D, 2D-NMR spectra and HR-ESI-MS. Impecylone A could selectivity inhibit HepG2 and A549 cell lines. The compound could induce apoptosis of A549 and arrest the cell cycle at G2/M phase in a dose-dependent manner. Conclusion: Impecylone A is a novel compound from Patrinia villosa Juss and could be a potential antitumor agent especially in the cell lines of A549.

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.

The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression

2005 ◽  
Vol 224 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Grit Kasper ◽  
Anke Vogel ◽  
Irina Klaman ◽  
Jörn Gröne ◽  
Iver Petersen ◽  
...  
Keyword(s):  
Functional Role ◽  
Tumour Progression ◽  
Solid Tumours ◽  
Dual Functional

scholarly journals The Bromodomain Inhibitor N-Methyl pyrrolidone Prevents Osteoporosis and BMP-Triggered Sclerostin Expression in Osteocytes

2018 ◽  
Vol 19 (11) ◽  
pp. 3332 ◽  
Author(s):  
Barbara Siegenthaler ◽  
Chafik Ghayor ◽  
Bebeka Gjoksi-Cosandey ◽  
Nisarat Ruangsawasdi ◽  
Franz Weber
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Osteoporosis Treatment ◽  
Estrogen Deficiency ◽  
Bone Morphogenetic Protein 2 ◽  
Protein Levels ◽  
Osteoporosis Management ◽  
Promising Target

(1) Background: In an adult skeleton, bone is constantly renewed in a cycle of bone resorption, followed by bone formation. This coupling process, called bone remodeling, adjusts the quality and quantity of bone to the local needs. It is generally accepted that osteoporosis develops when bone resorption surpasses bone formation. Osteoclasts and osteoblasts, bone resorbing and bone forming cells respectively, are the major target in osteoporosis treatment. Inside bone and forming a complex network, the third and most abundant cells, the osteocytes, have long remained a mystery. Osteocytes are responsible for mechano-sensation and -transduction. Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management. (2) Methods: Recently we showed in vitro and in vivo that NMP (N-Methyl-2-pyrrolidone) is a bioactive drug enhancing the BMP-2 (Bone Morphogenetic Protein 2) induced effect on bone formation while blocking bone resorption. Here we tested the effect of NMP on the expression of osteocyte-derived sclerostin. (3) Results: We found that NMP significantly decreased sclerostin mRNA and protein levels. In an animal model of osteoporosis, NMP prevented the estrogen deficiency-induced increased expression of sclerostin. (4) Conclusions: These results support the potential of NMP as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes.

scholarly journals Functional Role of the Cytoplasmic Tail Domain of the Major Envelope Fusion Protein of Group II Baculoviruses

2006 ◽  
Vol 80 (22) ◽  
pp. 11226-11234 ◽  
Author(s):  
Gang Long ◽  
Xiaoyu Pan ◽  
Marcel Westenberg ◽  
Just M. Vlak
Keyword(s):  
Fusion Proteins ◽  
Functional Role ◽  
Cytoplasmic Tail ◽  
Viral Envelope ◽  
Repair System ◽  
Dependent Manner ◽  
Tail Domain ◽  
F Protein ◽  
Group Ii

ABSTRACT F proteins from baculovirus nucleopolyhedrovirus (NPV) group II members are the major budded virus (BV) viral envelope fusion proteins. They undergo furin-like proteolysis processing in order to be functional. F proteins from different baculovirus species have a long cytoplasmic tail domain (CTD), ranging from 48 (Spodoptera litura multicapsid NPV [MNPV]) to 78 (Adoxophyes honmai NPV) amino acid (aa) residues, with a nonassigned function. This CTD is much longer than the CTD of GP64-like envelope fusion proteins (7 aa), which appear to be nonessential for BV infectivity. Here we have investigated the functional role of the CTD of Helicoverpa armigera single-capsid NPV (HearNPV), a group II NPV. We combined a newly constructed HearNPV f-null bacmid knockout-repair system and an Autographa californica MNPV (AcMNPV) gp64-null bacmid knockout-pseudotype system with mutation and rescue experiments to study the functional role of the baculovirus F protein CTD. We show that except for the 16 C-terminal aa, the HearNPV F CTD is essential for virus spread from cell to cell. In addition, the CTD of HearNPV F is involved in BV production in a length-dependent manner and is essential for BV infectivity. The tyrosine residue Y658, located 16 aa from the C terminus, seems to be critical. However, HearNPV F without a CTD still rescues the infectivity of gp64-null AcMNPV BV, indicating that the CTD is not involved in processing and fusogenicity. Altogether, our results indicate that the F protein is essential for baculovirus BV infectivity and that the CTD is important for F protein incorporation into BV.

scholarly journals Ultrasonic Extraction of Bioactive Compounds From Green Soybean Pods and Application in Green Soybean Milk Antioxidants Fortification

2021 ◽  
Author(s):  
Noppol Leksawasdi ◽  
Siraphat Taesuwan ◽  
Trakul Prommajak ◽  
Charin Techapun ◽  
Rattanaporn Khonchaisri ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Bioactive Compounds ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Bioactive Compound ◽  
Natural Antioxidants ◽  
Dependent Manner ◽  
Ultrasound Technique ◽  
Antioxidant Power ◽  
Soybean Milk

Abstract Green soybean (Glycine max L.) pods (GSP) are agro-industrial waste from the production of frozen green soybean and milk. These pods contain natural antioxidants and various bioactive compounds that are still underutilized. Polyphenols and flavonoids in GSP were extracted by ultrasound techniques and used in antioxidant fortification of green soybean milk. The ultrasound extraction that yielded the highest total polyphenol content was 50% amplitude for 10 min, whereas maximum flavonoids content was obtained at 50% amplitude for 15 min. Radical scavenging activity assayed by 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant power (FRAP) methods did not differ significantly (p>0.05) between the two conditions. Response surface methodology was applied to analyze an optimum ultrasonic-assisted extraction (UAE) condition of these variables. The highest desirability was found to be 50% amplitude with extraction time of 12.5 min. Fortification of the GSP extracts (1-3% v/v) in green soybean milk resulted in higher levels of bioactive compounds and antioxidant activity in a dose-dependent manner. Procyanidins were found to be the main polyphenols in dried GSP which were present at the concentration of 104.1 ± 2.1 mg/g dry sample, respectively. Addition of GSP extracts obtained by using an ultrasound technique to green soybean milk increased its bioactive compound content especially procyanidins as well as its antioxidant activity.

scholarly journals Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-Derived Osteoblasts

2020 ◽  
Vol 7 (1) ◽  
pp. 12 ◽  
Author(s):  
Robert Owen ◽  
Hossein Bahmaee ◽  
Frederik Claeyssens ◽  
Gwendolen C. Reilly
Keyword(s):  
Tissue Engineering ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Lithium Chloride ◽  
Osteoporosis Treatment ◽  
Bone Morphogenetic Protein 2 ◽  
Calcium Deposition ◽  
Matrix Deposition ◽  
Alp Activity

There is variability in the reported effects of compounds on osteoblasts arising from differences in experimental design and choice of cell type/origin. This makes it difficult to discern a compound’s action outside its original study and compare efficacy between compounds. Here, we investigated five compounds frequently reported as anabolic for osteoblasts (17β-estradiol (oestrogen), icariin, lactoferrin, lithium chloride, and menaquinone-4 (MK-4)) on human mesenchymal progenitors to assess their potential for bone tissue engineering with the aim of identifying a potential alternative to expensive recombinant growth factors such as bone morphogenetic protein 2 (BMP-2). Experiments were performed using the same culture conditions to allow direct comparison. The concentrations of compounds spanned two orders of magnitude to encompass the reported efficacious range and were applied continuously for 22 days. The effects on the proliferation (resazurin reduction and DNA quantification), osteogenic differentiation (alkaline phosphatase (ALP) activity), and mineralised matrix deposition (calcium and collagen quantification) were assessed. Of these compounds, only 10 µM MK-4 stimulated a significant anabolic response with 50% greater calcium deposition. Oestrogen and icariin had no significant effects, with the exception of 1 µM icariin, which increased the metabolic activity on days 8 and 22. 1000 µg/mL of lactoferrin and 10 mM lithium chloride both significantly reduced the mineralised matrix deposition in comparison to the vehicle control, despite the ALP activity being higher in lithium chloride-treated cells at day 15. This demonstrates that MK-4 is the most powerful stimulant of bone formation in hES-MPs of the compounds investigated, highlighting its potential in bone tissue engineering as a method of promoting bone formation, as well as its prospective use as an osteoporosis treatment.

scholarly journals Vitamin A and bone formation. Effect of an excess of retinol on bone collagen synthesis in vitro

1985 ◽  
Vol 226 (3) ◽  
pp. 789-795 ◽  
Author(s):  
I Dickson ◽  
J Walls
Keyword(s):  
Bone Formation ◽  
Collagen Synthesis ◽  
Bone Collagen ◽  
Dependent Manner ◽  
Stimulate Bone Resorption ◽  
Dna And Rna ◽  
A Cell ◽  
Dose Dependent ◽  
Bone Collagen Synthesis

The influence of an excess of retinol on bone formation was studied by using cultures of embryonic-chick calvaria. Retinol decreased collagen synthesis in a dose-dependent manner, non-collagenous protein synthesis being relatively unaffected. Collagen synthesis was significantly inhibited after 24 h of culture with retinol and was progressively decreased, compared with control cultures containing no retinol, as the period of culture was increased. The effect of retinol on collagen synthesis could be reversed by incubation of calvaria for further periods in retinol-free medium. Incorporation of [3H]thymidine and [3H]uridine into DNA and RNA respectively was not altered by culturing calvaria with retinol for 22 h. These latter findings, and the selectivity for collagen synthesis, all suggested that the effect observed was not a cell-toxicity phenomenon. The effect of retinol on collagen synthesis by chick calvarial osteoblasts was probably direct and not mediated by osteoclasts, since a negligible number of the latter cells is present in chick calvaria. In cultures of neonatal murine calvaria, which contain many osteoclasts, retinol similarly inhibited synthesis of collagen, but not of non-collagenous protein; the concentrations of retinol necessary to produce the response were similar to those required to stimulate bone resorption in vitro.

Antioxidant and Antiproliferative Activities of Crossostephium chinensis (L.) Makino

2009 ◽  
Vol 37 (04) ◽  
pp. 797-814 ◽  
Author(s):  
Tien-Ning Chang ◽  
Guan-Jhong Huang ◽  
Yu-Lin Ho ◽  
Shyh-Shyun Huang ◽  
Heng-Yuan Chang ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Bioactive Compound ◽  
Natural Antioxidants ◽  
Dependent Manner ◽  
Total Polyphenol ◽  
Human Hepatoma Hepg2 Cells ◽  
Hepatoma Hepg2 ◽  
Antiproliferative Activities

Crossostephium chinensis (L.) (CC) Makino is a common traditional Chinese medicinal plant used to dehumidify and cure rheumatism and arthralgia. The water and methanol extracts of C. chinensis (CCW and CCM) were evaluated for their antioxidant and antiproliferative activities. The antioxidant activities of CC were evaluated by using ABTS radical scavenging, DPPH radical scavenging, nitric oxide scavenging and superoxide scavenging methods. Iron chelating activity, lipid peroxidation, total polyphenol contents, total flavonoid contents and total flavonol contents were also detected. In all the tested models, both CCW and CCM showed their ability to scavenge the free radicals in a does-dependent manner. CCW had higher antioxidant and antiproliferative activities than CCM. In LC-MS-MS analysis, the chromatograms of CCW with good antioxidant activities were established. Rutin might be an important bioactive compound in CCW. The antiproliferative activities of CCW and CCM were also studied in vitro by using human hepatoma HepG2 cells. CCW exhibited good antiproliferative activity. These results indicated that CCW might be used as a potential source of natural antioxidants and as an anti-tumor agent.

scholarly journals α1G T-type calcium channel determines the angiogenic potential of pulmonary microvascular endothelial cells

2019 ◽  
Vol 316 (3) ◽  
pp. C353-C364 ◽  
Author(s):  
Zhen Zheng ◽  
Hairu Chen ◽  
Peilin Xie ◽  
Carol A. Dickerson ◽  
Judy A. C. King ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Functional Role ◽  
Transient Receptor Potential ◽  
Network Formation ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Channel Blockade ◽  
Angiogenic Potential ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Pulmonary microvascular endothelial cells (PMVECs) display a rapid angioproliferative phenotype, essential for maintaining homeostasis in steady-state and promoting vascular repair after injury. Although it has long been established that endothelial cytosolic Ca2+ ([Ca2+]i) transients are required for proliferation and angiogenesis, mechanisms underlying such regulation and the transmembrane channels mediating the relevant [Ca2+]i transients remain incompletely understood. In the present study, the functional role of the microvascular endothelial site-specific α1G T-type Ca2+ channel in angiogenesis was examined. PMVECs intrinsically possess an in vitro angiogenic “network formation” capacity. Depleting extracellular Ca2+ abolishes network formation, whereas blockade of vascular endothelial growth factor receptor or nitric oxide synthase has little or no effect, suggesting that the network formation is a [Ca2+]i-dependent process. Blockade of the T-type Ca2+ channel or silencing of α1G, the only voltage-gated Ca2+ channel subtype expressed in PMVECs, disrupts network formation. In contrast, blockade of canonical transient receptor potential (TRP) isoform 4 or TRP vanilloid 4, two other Ca2+ permeable channels expressed in PMVECs, has no effect on network formation. T-type Ca2+ channel blockade also reduces proliferation, cell-matrix adhesion, and migration, three major components of angiogenesis in PMVECs. An in vivo study demonstrated that the mice lacking α1G exhibited a profoundly impaired postinjury cell proliferation in the lungs following lipopolysaccharide challenge. Mechanistically, T-type Ca2+ channel blockade reduces Akt phosphorylation in a dose-dependent manner. Blockade of Akt or its upstream activator, phosphatidylinositol-3-kinase (PI3K), also impairs network formation. Altogether, these findings suggest a novel functional role for the α1G T-type Ca2+ channel to promote the cell’s angiogenic potential via a PI3K-Akt signaling pathway.

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