scholarly journals Does Nimodipine, a Selective Calcium Channel Blocker, Impair Chondrocyte Proliferation or Damage Extracellular Matrix Structures?

2019 ◽  
Vol 20 (6) ◽  
pp. 517-524
Author(s):  
Necati Kaplan ◽  
Ibrahim Yilmaz ◽  
Numan Karaarslan ◽  
Yasin E. Kaya ◽  
Duygu Y. Sirin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Active Ingredient ◽  
Cellular Proliferation ◽  
Hypoxia Inducible Factor ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Control Group ◽  
Chondrocyte Proliferation ◽  
Hypoxia Inducible Factor 1 ◽  
Col2a1 Expression

Background: The study aimed to investigate the effects of the active ingredient, nimodipine, on chondrocyte proliferation and extracellular matrix (ECM) structures in cartilage tissue cells. Methods: Chondrocyte cultures were prepared from tissues resected via surgical operations. Nimodipine was then applied to these cultures and molecular analysis was performed. The data obtained were statistically calculated. Results: Both, the results of the (3-(4,5 dimethylthiazol2-yl)-2,5-diphenyltetrazolium (MTT) assay and the fluorescence microscope analysis [a membrane permeability test carried out with acridine orange/ propidium iodide staining (AO/PI)] confirmed that the active ingredient, nimodipine, negatively affects the cell cultures. Conclusion: Nimodipine was reported to suppress cellular proliferation; chondroadherin (CHAD) and hypoxia-inducible factor-1 alpha (HIF-1α) expression thus decreased by 2.4 and 1.7 times, respectively, at 24 hrs when compared to the control group (p < 0.05). Furthermore, type II collagen (COL2A1) expression was not detected (p<0.05). The risk that a drug prescribed by a clinician in an innocuous manner to treat a patient by relieving the symptoms of a disease may affect the proliferation, differentiation, and viability of other cells and/or tissues at the molecular level, beyond its known side effects or adverse events, should not be forgotten.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

scholarly journals Hyperbaric Oxygen (HBO) Reduce Expression of Hypoxia Inducible Factor-1 Alpha (HIF-1 alpha) and Endometriotic Tissue Size in Mice Model of Endometriosis

2020 ◽  
Vol 151 ◽  
pp. 01003
Author(s):  
Dedy Syahrizal ◽  
Cut Mustika ◽  
Teuku Renaldi ◽  
Mohammad G. Suryokusumo ◽  
Hendy Hendarto
Keyword(s):  
Hyperbaric Oxygen ◽  
Hypoxia Inducible Factor ◽  
Control Group ◽  
Mice Model ◽  
Control Group Design ◽  
Hypoxia Inducible Factor 1 ◽  
Peritoneal Tissue ◽  
Implant Size ◽  
Experimental Laboratory ◽  
Tissue Size

Hypoxia in endometriosis will increase the expression of Hypoxia Inducible Factor-1alpha (HIF1alpha) and its expression could be decreased by Hyperbaric Oxygen (HBO). This study aimed to analyze the effect of HBO 2.4 ATA for 3x30 minutes per day for 10 days on the expression of HIF-1 alpha and endometriotic tissue size on mice model of endometriosis. This study was an experimental laboratory study with a separate pretest-posttest control group design. The mice were divided into three groups, the first was a pretest control group (which describes the condition after endometrium transplantation), the second was the endometriotic group that received hyperbaric oxygen, and the third was the endometriotic group that did not receive hyperbaric oxygen therapy. The endometriosis implant size in the peritoneal tissue was assessed and the immunohistochemistry examination was conducted to determine the expression of HIF-1 alpha. The endometriosis tissue size was reduced in the HBO group compared to the control and nonHBO group. The lowest expression of HIF-1 alpha was significantly found in HBO over the other group. The decrease of HIF1 alpha expression mediates the reduction of size endometriotic tissue due to the therapy of HBO.

scholarly journals Hypoxia Inducible Factor-1-Alpha Expression on Preeclampsia Mice Model With L-Arginine Administration

2021 ◽  
Vol 57 (3) ◽  
pp. 226
Author(s):  
Nutria Widya Purna Anggraini ◽  
Sri Sulistyowati ◽  
Muhammad Adrianes Bachnas ◽  
Eric Edwin Yuliantara ◽  
Wisnu Prabowo ◽  
...  
Keyword(s):  
Treatment Group ◽  
Statistical Tests ◽  
Hypoxia Inducible Factor ◽  
Data Distribution ◽  
Hypoxic Condition ◽  
Control Group ◽  
Mice Model ◽  
Hypoxia Inducible Factor 1 ◽  
Minimum Value ◽  
Maximum Value

Preeclampsia is hypertension in pregnancy that affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. In the pathogenesis of preeclampsia, placental hypoxia plays an important role, associated with excessive trophoblast apoptosis resulting in decreased trophoblast and spiral arteries invasion. This placental hypoxic condition will induce increased expression of Hypoxia Inducible Factor -1-Alpha (HIF-1-A). L-Arginine is a potent vasodilator presumably to improve preeclampsia placental hypoxic conditions and reduce HIF-1-A expression. This study was an experimental study with a parallel-group post-test only design. Thirty-six preeclamptic mice models were divided into 2 groups. The control group (K1) 18 preeclamptic mice model without treatment and the treatment group (K2) 18 preeclamptic mice given L-Arginine. The independent variable was the administration of L-Arginine and the dependent variable is the placental HIF-1-A expression. Statistical analysis used unpaired t-test on normal data distribution, and Mann Whitney test on abnormal data distribution. The mean of placental HIF-1-A expression K1 was 2.47 ± 1.65 with a minimum value of 0.4 and a maximum value of 6.6. At K2 0.93 ± 0.55 with a minimum value of 0.0 and a maximum value of 2.0. Statistical tests showed that the placental HIF-1-A expression in the treatment group was significantly lower than that in the control group (p <0.001). In conclusion, the expression of HIF-1-A in preeclamptic mice model placenta decreased with L-Arginine administration.

244 CHONDROGENIC PELLET CULTURES FOR CARTILAGE TISSUE ENGINEERING GROW BY DEPOSITION OF MATRIX AND NOT BY CELLULAR PROLIFERATION

2016 ◽  
Vol 28 (2) ◽  
pp. 254 ◽  
Author(s):  
S. Johnson ◽  
D. Milner ◽  
H. Lopez-Lake ◽  
M. Wheeler
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Chondrogenic Differentiation ◽  
Cellular Proliferation ◽  
Cartilage Matrix ◽  
T Test ◽  
Cartilage Tissue ◽  
Matrix Deposition ◽  
Student’S T ◽  
Student’S T Test

Pellet cultures are commonly used to study chondrogenic differentiation in vitro. Our laboratory has demonstrated pellets made with chondrocytes grow in size during culture and produce cartilage matrix, but pellets made with adipose-derived mesenchymal stem cells (ASC) grow only slightly, producing little cartilage matrix. The objective of this study was to determine if differences in chondrocyte and ASC pellet growth result from differences in cell proliferation or in deposition of extracellular matrix. Primary chondrocytes and ASC from adult pigs were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum. To determine baseline proliferation rates in monolayer culture, cells were grown on coverslips in 10 µM bromodeoxyuridine (BrdU) for 24 h and immunostained for BrdU labelling. For pellet cultures, 5 × 105 cells were placed in 15 mL-conical tubes, pelleted by centrifugation in 1.0 mL of chondrogenic base media (CBM: DMEM + 40 µg mL–1 of proline, 50 µM ascorbic acid-2-phosphate, 100 nM dexamethasone, and 1× insulin-transferrin-selenium), and cultured in CBM for 1, and 4 weeks. To detect proliferation in pellets, 1- and 2-week cultured samples were labelled with 10 µM BrdU for 24 h before harvest. Pellets were fixed with 4% paraformaldehyde, embedded, and sectioned on a Leica CM1900 cryostat (Leica Microsystems, Wetzlar, Germany). To assess chondrogenic differentiation and matrix expression, sections were stained for collagen II, keratin sulfate, and chondroitin sulfate. Images were captured and distance between adjacent nuclei in 1- and 4-week pellets were measured using Zeiss imaging software. As expected, cells on coverslips showed BrdU labelling, with higher labelling in ASC cultures indicating faster proliferation (n = 5, 77.3 ± 3.74% chondrocyte v. 92.1 ± 2.88% ASC; α = 0.05; P < 0.0001; Student’s t-test). However, BrdU labelling was not seen in sections from ASC or chondrocyte pellets (n = 5), at either 1 or 2 weeks. Absence of cellular proliferation in pellets was verified by negative staining for the mitotic marker Aurora KinaseB (AurKB). Cartilage matrix staining was strong in chondrocyte pellets at all time points and absent in ASC pellets. Cell nuclei were closely packed in both ASC and chondrocyte pellets at 1 week, but a significant increase in distance between adjacent nuclei with interspersed matrix staining was noted in chondrocyte pellets at 4 weeks (n = 4, 11.88 ± 0.67 µm at 1 week v. 26.85 ± 2.06 µm at 4 weeks; α = 0.05; P < 0.0001; Student’s t-test). As TGFβ3 has been shown to induce chondrogenesis in ASC, ASC pellets were cultured in CBM + 10 ng of TGFβ3 for 1 and 2 weeks (n = 4). The TGFβ3 treatment did not induce cell proliferation in pellets, as sections were negative for BrdU. However, expression of cartilage markers keratan sulfate and chondroitin were noted. Based on our data, neither ASC nor chondrocytes proliferate in pellet culture, and chondrocyte pellet growth is due to extracellular matrix deposition.

Participation of HIF-1 in the mechanisms of neuroadaptation to acute stressful exposure

2021 ◽  
Vol 19 (2) ◽  
pp. 183-188
Author(s):  
Andrey V. Lyubimov ◽  
Platon P. Khokhlov
Keyword(s):  
Prefrontal Cortex ◽  
Hypoxia Inducible Factor ◽  
Control Group ◽  
Behavioral Reactions ◽  
Hypoxia Inducible Factor 1 ◽  
Adaptive Capabilities ◽  
Pathogenic Factors ◽  
Mechanisms Of Adaptation ◽  
The Brain ◽  
Positive Effect

BACKGROUND: New laboratory and instrumental technologies for analyzing the adaptive capabilities of a biological organism to acute stressful effects including hypoxic ones have significantly facilitated the diagnosis and fixation of adaptive behavioral reactions, physiological and biochemical changes. Much attention has been paid to the phenomenon of preconditioning a positive effect from exposure to small doses of pathogenic factors. Hypoxia-inducible factor 1 (HIF-1) is one of the most promising markers for fixing the phenomenon of hypoxic preconditioning. AIM: To study the mechanisms of neuroadaptation to acute stressful effects. MATERIALS AND METHODS: Using models of immobilization, hypothermic exposure, and electrocutaneous irritation of rat paws were carried out for the assessment of the mechanisms of neuroadaptation. Changes in the HIF-1 concentration were recorded in the blood and in the structures of the brain. RESULTS: The maximum concentration of HIF-1 was found in the amygdala (230 pg / mg), in the prefrontal cortex it was 50.8 pg / mg in the control group. Hypothermal exposure increased the HIF-1 content in the amygdala by more than 4 times, while emotionally pain and immobilization showed a slight decrease in HIF-1 in the amygdala. All types of stressors significantly increased the concentration of HIF-1 in the prefrontal cortex of animals. The most pronounced changes were observed when using the model of emotional pain stress. The obtained experimental data allow us to draw with caution a conclusion about the universality and unity of multicomponent mechanisms of adaptation to acute stressful effects.

Association between hypoxia-inducible factor-1 alpha rs11549465 (1772 C>T) polymorphism and metabolic syndrome

2021 ◽  
pp. 1-15
Author(s):  
Uzma Zafar ◽  
Zaima Ali ◽  
Saba Khaliq ◽  
Khalid Lone
Keyword(s):  
Metabolic Syndrome ◽  
Hypoxia Inducible Factor ◽  
Control Group ◽  
Cross Sectional ◽  
Hypoxia Inducible Factor 1 ◽  
Increased Risk ◽  
Significant Difference ◽  
Venous Sample ◽  
In The Wild ◽  
The University

Abstract Objectives: To find the association of single nucleotide polymorphism of hypoxia-inducible factor-1 alpha, rs11549465 (1772 Cytosine > Thymine) with metabolic syndrome, and to compare the anthropometric and biochemical variables in different genotypes of hypoxia-inducible factor-1 alpha. Methods: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to April 2019, and comprised patients of metabolic syndrome selected from the Sheikh Zayed Hospital, Lahore. Healthy controls were also enrolled. Fasting venous sample was taken for the determination of study parameters. The genetic variant of hypoxia-inducible factor-1 alpha was analysed by restriction fragment length polymorphism polymerase chain reaction. Data was analysed using SPSS 22. Results: Out of 400 subjects, 200(50%) each were patients and controls. The frequency of CC genotype of hypoxia-inducible factor-1 alpha Cytosine > Thymine in patients was 166(83%) and in controls 147(73.5%); CT genotype was 34(17%) and 53(26.5%) respectively, while TT genotype was not observed. There was a significant association of the C allele and CC genotype (p=0.03) with the increased risk of metabolic syndrome (p=0.02). On comparison of study variables in the two genotypes, systolic blood pressure, anthropometric and lipid parameters were significantly higher in the wild CC genotype compared to CT in the control group (p<0.05), but there was no significant difference in the patients (p>0.05). Conclusion: Major allele C of hypoxia-inducible factor-1 alpha 1772 Cytosine > Thymine was found to be associated with increased risk of metabolic syndrome. Continuous...

Celecoxib Attenuates Cartilage Matrix Damage in Arthritis Rats by Inhibiting NF-κ B

2020 ◽  
Vol 10 (4) ◽  
pp. 531-537
Author(s):  
Lukuan Du ◽  
Zhenghui Jiang ◽  
Zhaohui Wang ◽  
Liming Wang
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Culture Supernatant ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protein Expressions ◽  
Col2a1 Expression ◽  
Matrix Damage

Objective: Celecoxib selectively inhibits the activity of COX-2 and the production of prostaglandin (PG), and plays a therapeutic role in treating osteoarthritis (OA). NF-κB signaling and IL-1α and TNFα are involved in OA pathogenesis. This study explored whether Celecoxib might exert therapeutic effects on OA through regulating NF-κB signaling and IL-1β and TNF release in OA rat model. Method : The contents of MMP-13, Hyp, IL-1β and TNFα in synovial fluid were detected by ELISA. The protein expressions of NF-κ B p-p65, COL2A1 and the activity of caspase-3 were detected. OA model rats were separated into OA group and OA+ Celecoxib group followed by analysis of MMP-13, Hyp, IL-1β and TNF level in articular fluid by ELISA and p-p65 and COL2A1 level and caspase-3 activity by western blot. Rat cartilage tissue was cultured and divided into control group, LPS group and LPS+ Celecoxib group followed by analysis of expressions of p-p65 and COL2A1 in cartilage tissue, IL-1 and TNF content in culture supernatant, and chondrocyte apoptosis. Results: Compared with Sham group, p-p65 expression and caspase-3 activity in cartilage tissue of OA rats was increased and COL2A1 level was reduced. Meanwhile the expression of MMP-13, Hyp, IL-1β and TNF in articular fluid of OA rats was increased. Compared to OA group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in OA+ Celecoxib treatment group along with decreased MMP-13, Hyp, IL-1β and TNF level in articular fluid. p-p65 expression and caspase-3 activity in LPS group was increased and COL2A1 expression was decreased with increased IL-beta; and TNF content. Compared to LPS group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in LPS+ Celecoxib group with decreased content of IL-1β and TNFα. Conclusion: Celecoxib can protect cartilage in OA by inhibiting NF-κB activation and IL-1β and TNF release, and decreasing cell apoptosis in inflammatory environment.

scholarly journals Effect of Hypoxia-Inducible Factor 1α on Early Healing in Extraction Sockets

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Hyun-Chang Lim ◽  
Daniel S. Thoma ◽  
Mijeong Jeon ◽  
Je-Seon Song ◽  
Sang-Kyou Lee ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Treatment Modalities ◽  
Control Group ◽  
Collagen Membrane ◽  
Bovine Bone ◽  
Hypoxia Inducible Factor 1 ◽  
Early Healing ◽  
Bovine Bone Mineral ◽  
Deproteinized Bovine Bone Mineral ◽  
Apical Area

The aim of the present study was to investigate the effect of hypoxia-inducible factor 1α (HIF1A) on the early healing (4 weeks) of extraction sockets exhibiting partial loss of the labial bone. Two extraction sockets of the maxillary incisors from each of six dogs were assigned to two treatment modalities: deproteinized bovine bone mineral (i) with 10% collagen (DBBM-C) soaked with HIF1A and covered by a collagen membrane (CM) (HIF group) or (ii) treated with DBBM-C only and covered by a CM (control group). Microcomputed tomography revealed some degree of collapse of the labial contour. The totally augmented volume and new bone volume did not differ significantly between two groups (P>0.05). The histological analysis revealed that the apical area of the socket was mostly filled with newly formed bone, while there was less newly formed bone in the coronal area and incomplete cortex formation. The histomorphometric analysis revealed that the area of newly formed bone was significantly larger in the HIF group than the control group (12.16±3.04 versus 9.48±2.01 mm2, P<0.05), while there was no significant intergroup difference in the total augmented area. In conclusion, even though DBBM-C soaked with HIF1A enhanced histomorphometric bone formation, this intervention did not demonstrate superiority in preventing ridge shrinkage compared to DBBM-C alone. Clinical relevance of these findings should be further studied.

Recombinant human type II collagen as a material for cartilage tissue engineering

2008 ◽  
Vol 31 (11) ◽  
pp. 960-969 ◽  
Author(s):  
H.J. Pulkkinen ◽  
V. Tiitu ◽  
P. Valonen ◽  
E.-R. Hämäläinen ◽  
M.J. Lammi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Confocal Microscopy ◽  
Cartilage Tissue Engineering ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Homogeneous Distribution ◽  
Type Ii ◽  
Human Type ◽  
Cultivation Period

Purpose Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro. Methods Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays. Results Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week. Conclusion Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.

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