Pamidronic acid-grafted nHA/PLGA hybrid nanofiber scaffolds suppress osteoclastic cell viability and enhance osteoblastic cell activity

2016 ◽  
Vol 4 (47) ◽  
pp. 7596-7604 ◽  
Author(s):  
Adnan Haider ◽  
Davy-louis Versace ◽  
Kailash Chandra Gupta ◽  
Inn-Kyu Kang
Keyword(s):  
Bone Resorption ◽  
Cell Viability ◽  
Pamidronic Acid ◽  
Cell Activity ◽  
Osteoblastic Cell ◽  
Osteoclast Activity ◽  
Nanofiber Scaffolds ◽  
Hybrid Nanofiber ◽  
Osteoclastic Cell

Controlling osteoclast activity helps in prevention of bone resorption.

Decreased potassium stimulates bone resorption

1997 ◽  
Vol 272 (6) ◽  
pp. F774-F780 ◽  
Author(s):  
D. A. Bushinsky ◽  
D. R. Riordon ◽  
J. S. Chan ◽  
N. S. Krieger
Keyword(s):  
Bone Resorption ◽  
Collagen Synthesis ◽  
Cell Activity ◽  
Bone Cell ◽  
Osteoblastic Cell ◽  
Enzyme Release ◽  
Osteoblastic Cell Line ◽  
Glucuronidase Activity ◽  
K Concentration ◽  
Low K

Metabolic acidosis induces net calcium efflux (JCa+) from cultured bone, in part, through an increase in osteoclastic resorption and a decrease in osteoblastic formation. In humans provision of base as potassium (K+) citrate, but not sodium (Na+) citrate, reduces urine Ca (UCa), and oral KHCO3 decreases bone resorption and UCa in postmenopausal women. Potassium deprivation alone leads to an increase in UCa. To determine whether decreased extracellular K+ concentration ([K+]) at a constant pH, PCO2, and [HCO-3] alters JCa+ and bone cell activity, we measured JCa+, osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured for 48 h in medium of varying [K+]. Calvariae were cultured in control medium (approximately 4 mM [K+]) or medium with mildly low K+ (MLK, approximately 3 mM [K+]), very low K+ (VLK, approximately 2 mM [K+]), or extremely low K+ (ELK, approximately 1 mM [K+]) (n > or = 9 in each group). Compared with control, ELK, but not MLK or VLK, resulted in a marked increase in JCa+ and an increase in beta-glucuronidase release and a decrease in collagen synthesis. JCa+ was correlated directly with medium beta-glucuronidase activity and inversely with collagen synthesis. To determine whether the reduction in medium [K+] was associated with a decrease in intracellular pH (pHi), we measured pHi in MC3T3-E1 cells, a mouse osteoblastic cell line. Incubation in 1 mM [K+] led to a significant decrease in pHi compared with 3 mM [K+]. Thus incubation in a reduced [K+] medium stimulates JCa+ and osteoclastic enzyme release and inhibits osteoblastic collagen synthesis, which may be mediated by a reduction in bone cell pH.

scholarly journals BMP-2 Grafted nHA/PLGA Hybrid Nanofiber Scaffold Stimulates Osteoblastic Cells Growth

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Adnan Haider ◽  
Sukyoung Kim ◽  
Man-Woo Huh ◽  
Inn-Kyu Kang
Keyword(s):  
Targeted Delivery ◽  
Bone Tissue Regeneration ◽  
Osteoblastic Cells ◽  
Osteoblastic Cell ◽  
Spectroscopic Techniques ◽  
Nanofiber Scaffold ◽  
Morphogenetic Protein ◽  
Nanofiber Scaffolds ◽  
Hybrid Nanofiber

Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/degenerated tissues or organs. Natural bone is a hierarchical structure, comprised of various cells having specific functions that are regulated by sophisticated mechanisms. However, the regulation of the normal functions in damaged or injured cells is disrupted. In order to address this problem, we attempted to artificially generate a scaffold for mimicking the characteristics of the extracellular matrix at the nanoscale level to trigger osteoblastic cell growth. For this purpose, we have chemically grafted bone morphogenetic protein (BMP-2) onto the surface of L-glutamic acid modified hydroxyapatite incorporated into the PLGA nanofiber matrix. After extensive characterization using various spectroscopic techniques, the BMP-g-nHA/PLGA hybrid nanofiber scaffolds were subjected to variousin vitrocytocompatibility tests. The results indicated that BMP-2 on BMP-g-nHA/PLGA hybrid nanofiber scaffolds greatly stimulated osteoblastic cells growth, contrary to the nHA/PLGA and pristine PLGA nanofiber scaffold, which are used as control. These results suggest that BMP-g-nHA/PLGA hybrid nanofiber scaffold can be used as a nanodrug carrier for the controlled and targeted delivery of BMP-2, which will open new possibilities for enhancing bone tissue regeneration and will help in the treatment of various bone-related diseases in the future.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

Tamoxifen inhibits phorbol ester stimulated osteoclastic bone resorption: An effect mediated by calmodulin

2000 ◽  
Vol 78 (6) ◽  
pp. 715-723 ◽  
Author(s):  
John P Williams ◽  
Margaret A McKenna ◽  
Allyn M Thames III ◽  
Jay M McDonald
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Bone Resorption ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Fold Increase ◽  
Dependent Manner ◽  
Osteoclast Activity ◽  
Kinase C ◽  
Protein Kinase Cα

Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the phorbol ester, phorbol myristate acetate, on osteoclast activity. Phorbol esters stimulate bone resorption and calmodulin levels four-fold (k0.5 = 0.1–0.3 µM). In contrast, tamoxifen inhibited osteoclast activity ~60% with an IC50 of 1.5 µM, had no apparent effect on protein kinase C activity in whole-cell lysates, and reduced protein kinase Cα recovered by immunoprecipitation 75%. Phorbol esters stimulated resorption in a time-dependent manner that was closely correlated with a similar-fold increase in calmodulin. Protein kinase Cα, β, δ, ε, and ζ were all down-regulated in response to phorbol ester treatment. Tamoxifen and trifluoperazine inhibited PMA-dependent increases in bone resorption and calmodulin by 85 ± 10%. Down-regulation of protein kinase C isoforms by phorbol esters suggests that the observed increases in bone resorption and calmodulin levels are most likely due to a mechanism independent of protein kinase C and dependent on calmodulin. In conclusion, the data suggest that protein kinase C negatively regulates calmodulin expression and support the hypothesis that the effects of both phorbol esters and tamoxifen on osteoclast activity is mediated by calmodulin.Key words: osteoclast, calmodulin, tamoxifen, osteoporosis, protein kinase C.

scholarly journals Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Seokyung Shin ◽  
Ki Jun Kim ◽  
Hye Jeong Hwang ◽  
Sewon Noh ◽  
Ju Eun Oh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Mouse Model ◽  
Cell Viability ◽  
Nk Cell ◽  
Cell Activity ◽  
Tumor Burden ◽  
Control Group ◽  
Nk Cell Activity ◽  
Dexmedetomidine Infusion

BackgroundThe surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model.MethodsThe effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery.ResultsDexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P<0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P<0.001) and the in vivo imaging system (P=0.03).ConclusionsDexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.

scholarly journals miR-124-3p Inhibits Microglial Secondary Inflammation After Basal Ganglia Hemorrhage by Targeting TRAF6 and Repressing the Activation of NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yudan Fang ◽  
Xiaoqin Hong
Keyword(s):  
Basal Ganglia ◽  
Cell Viability ◽  
Healthy Volunteers ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Expression Patterns ◽  
Cell Activity ◽  
Inflammatory Factors ◽  
High Morbidity ◽  
Apoptosis Rate

Objectives: Intracerebral hemorrhage (ICH) represents a serious central nervous system emergency with high morbidity and mortality, and the basal ganglia is the most commonly affected brain region. Differentially expressed microRNAs (miRs) have recently been highlighted to serve as potential diagnostic biomarkers and therapeutic targets for ICH. This study investigated the mechanism of miR-124-3p in microglial secondary inflammation after ICH.Methods: In this study, 48 patients with primary basal ganglia ICH and 48 healthy volunteers were selected and venous blood was collected from all patients on the second morning of admission (within 24 h of stroke onset). The expression of miR-124-3p in serum was detected by RT-qPCR. Three months after ICH, the patients were assessed by modified Rankin Scale (mRS), and the correlation between miR-124-3p expression and mRS score was analyzed by Pearson. The inflammatory response of microglia was induced by lipopolysaccharide (LPS) to establish the cell model of microglial inflammation. miR-124-3p expression patterns were detected in the serum of ICH patients and healthy volunteers, normal microglia, and LPS-induced microglia. The miR-124-3p mimic was transfected into LPS-induced microglia, followed by measurement of the inflammatory factors, apoptosis rate, and cell viability. The target gene of miR-124-3p was predicted and verified. The expression patterns of tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected. pcDNA3.1 and pcDNA3.1-TRAF6 were transfected into LPS-induced HMC3 cells, and nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain-containing 3 (NLRP3) expression patterns were determined. Lastly, the effects of TRAF6 overexpression on apoptosis, cell viability, and inflammation in HMC3 cells were measured.Results: miR-124-3p was downregulated in the serum of basal ganglia ICH patients and LPS-induced microglia, and miR-124-3p expression was negatively correlated with mRS. Overexpression of miR-124-3p reduced the inflammatory factors and apoptosis rate and promoted cell activity in LPS-induced microglia. miR-124-3p was found to target TRAF6. Overexpression of TRAF6 enhanced the expression of NLRP3 inflammasome, inflammatory factors and apoptosis rate, and reduced cell viability.Conclusion: Our findings indicate that miR-124-3p repressed the activation of NLRP3 inflammasome by targeting TRAF6, thus inhibiting microglial secondary inflammation after ICH in basal ganglia.

scholarly journals Neural precursor cells/dopamine neuron direct conversion using hybrid nanofiber scaffolds

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S303-S304
Author(s):  
Seunghwan Ko ◽  
Mi-Sun Lim ◽  
Sang-Mi Kim ◽  
Keesung Kim ◽  
Chang-Hwan Park
Keyword(s):  
Direct Conversion ◽  
Precursor Cells ◽  
Dopamine Neuron ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Nanofiber Scaffolds ◽  
Hybrid Nanofiber

scholarly journals Chlorogenic acid protects PC12 cells against corticosterone-induced neurotoxicity related to inhibition of autophagy and apoptosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaowen Shi ◽  
Nian Zhou ◽  
Jieyi Cheng ◽  
Xunlong Shi ◽  
Hai Huang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Chlorogenic Acid ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanism ◽  
Cell Activity ◽  
Neuronal Cell ◽  
Mtor Signaling ◽  
Specific Marker ◽  
Mtor Signaling Pathway

Abstract Background There are evidences that chlorogenic acid (CGA) has antidepressant effects, however the underlying molecular mechanism has not been well understood. The aim of the study was to explore the neuroprotective effect of CGA on corticosterone (CORT)-induced PC 12 cells and its mechanism, especially the autophagy pathway. Methods PC12 cells were incubated with CORT (0, 100, 200, 400 or 800 μM) for 24 h, cell viability was measured by MTT assay. PC12 cells were cultured with 400 μM of CORT in the absence or presence of CGA (25 μg/ml) for 24 h, morphologies and specific marker of autophagosome were observed by transmission electron microscope (TEM) and confocal immunofluorescence microscopy, respectively. In addition, PC12 cells were treated with different doses of CGA (0, 6.25, 12.5, 25 or 50 μg/ml) with or without CORT (400 μM) for 24 h, cell viability and changes in the morphology were observed, and further analysis of apoptotic and autophagic proteins, and expression of AKT/mTOR signaling pathway were carried out by Western blot. Specific inhibitors of autophagy 3-Methyladenine (3-MA) and chloroquine (CQ) were added to the PC12 cells cultures to explore the potential role of autophagy in CORT-induced neuronal cell apoptosis. Results Besides decreasing PC12 cell activity, CORT could also induce autophagy and apoptosis of PC12 cells, while CGA could reverse these effects. In addition, CGA treatment regulated AKT/mTOR signaling pathway in PC12 cells. CGA, similar to 3-MA and QC, significantly inhibited CORT-induced apoptosis in PC12 cells. Conclusions Our results provide a new molecular mechanism for the treatment of CORT-induced neurotoxicity by CGA, and suggest CGA may be a potential substance which is can alleviate depression.

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