scholarly journals Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo

2016 ◽  
Vol 13 (119) ◽  
pp. 20160337 ◽  
Author(s):  
Eimear B. Dolan ◽  
David Tallon ◽  
Wing-Yee Cheung ◽  
Mitchell B. Schaffler ◽  
Oran D. Kennedy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thermal Damage ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Cellular Damage ◽  
Sprague Dawley ◽  
Related Factors ◽  
Thermally Induced ◽  
Rat Tibia

Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures in vivo is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague–Dawley rat tibia were exposed to clinically relevant temperatures (47°C or 60°C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes ( Rankl , Opg and M-csf ), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production ( Cox2 ), vascularization ( Vegf ) and inflammatory ( Il1a ) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the in vivo effect of thermally induced osteocyte damage on the gene expression profile.

Recovery periods restore mechanosensitivity to dynamically loaded bone

2001 ◽  
Vol 204 (19) ◽  
pp. 3389-3399 ◽  
Author(s):  
Alexander G. Robling ◽  
David B. Burr ◽  
Charles H. Turner
Keyword(s):  
Bone Formation ◽  
Bone Cells ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Four Point Bending ◽  
Rat Tibia ◽  
Time Required ◽  
The Right

SUMMARY Bone cells are capable of sensing and responding to mechanical forces, but mechanosensitivity begins to decline soon after the stimulus is initiated. Under continued stimulation, bone is desensitized to mechanical stimuli. We sought to determine the amount of time required to restore mechanosensitivity to desensitized bone cells in vivo by manipulating the recovery time (0, 0.5, 1, 2, 4 or 8 h) allowed between four identical daily loading bouts. We also investigated the osteogenic effectiveness of shorter-term recovery periods, lasting several seconds (0.5, 3.5, 7 or 14 s), introduced between each of 36 identical daily loading cycles. Using the rat tibia four-point bending model, the right tibia of 144 adult female Sprague-Dawley rats was subjected to bending, sham bending or no loading. In the rats receiving recovery periods between loading bouts, histomorphometric measurements from the endocortical surface of the loaded and nonloaded control (left) tibiae revealed more than 100 % higher relative bone formation rates in the 8 h recovery group than in the 0 and 0.5 h recovery groups. Approximately 8 h of recovery was sufficient to restore full mechanosensitivity to the cells. In the rats allowed time to recover between load cycles, 14 s of recovery resulted in significantly higher (66–190 %) relative bone formation rates compared to any of the three shorter recovery periods. In both experiments, bone formation in the sham-bending animals was similar to that in the nonloaded control group. The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens.

scholarly journals Regulation of mdrlb gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro

1996 ◽  
Vol 17 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Barbara A. Hill ◽  
Paul C. Brown ◽  
Karl-Heinz Preisegger ◽  
Jeffrey A. Silverman
Keyword(s):  
Gene Expression ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Hyperglycemia modulates angiotensinogen gene expression

2001 ◽  
Vol 281 (3) ◽  
pp. R795-R802 ◽  
Author(s):  
Ilan Gabriely ◽  
Xiao Man Yang ◽  
Jane A. Cases ◽  
Xiao Hui Ma ◽  
Luciano Rossetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Biosynthetic Pathway ◽  
Fold Increase ◽  
Suppressive Effect ◽  
Sprague Dawley ◽  
Hexosamine Biosynthetic Pathway ◽  
Obese Rats ◽  
Agt Gene

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (∼300 g) and obese (∼450 g) Sprague-Dawley rats in four clamp studies ( n= 3/group), creating physiological hyperinsulinemia (∼60 μU/ml, by an insulin clamp), hyperglycemia (∼18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 μmol · kg−1 · min−1) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats ( P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient “pulses” may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.

Acute hypoxia stimulates renin secretion and renin gene expression in vivo but not in vitro

1997 ◽  
Vol 272 (4) ◽  
pp. R1105-R1111 ◽  
Author(s):  
T. Ritthaler ◽  
K. Schricker ◽  
F. Kees ◽  
B. Kramer ◽  
A. Kurtz
Keyword(s):  
Gene Expression ◽  
Acute Hypoxia ◽  
Primary Cultures ◽  
Renin Secretion ◽  
Plasma Norepinephrine ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Renin Gene ◽  
Renin Mrna

This study aimed at examining the influence of acute hypoxia on renin secretion and renin gene expression in the kidney. To this end, male Sprague-Dawley rats were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for 6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined. PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively. Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary cultures of renal juxtaglomerular cells had no influence on renin secretion and renin gene expression after 6 and 20 h. Our findings thus suggest that both arterial and venous hypoxia can be powerful stimulators of renin secretion and renin gene expression in vivo. Because renal denervation did not prevent stimulation of the renin system by hypoxia, the effect could be indirectly mediated via the baroreceptor-macula densa mechanism. Another potential mediator of the effect could be circulating catecholamines, since we found that plasma norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation, respectively.

scholarly journals Mechanism of protection of rat hepatocytes from acetaminophen-induced cellular damage by ethanol extract of Aerva lanata

2019 ◽  
Vol 12 (4) ◽  
pp. 169-179
Author(s):  
Chithambaram Sujatha Anusha ◽  
Hariharan Sini ◽  
Bhaskara Prakashkumar ◽  
Kottayath Govindan Nevin
Keyword(s):  
Liver Toxicity ◽  
Culture Media ◽  
Ethanol Extract ◽  
Cellular Damage ◽  
Control Group ◽  
Sprague Dawley ◽  
Group I ◽  
Aerva Lanata ◽  
Cox 1

AbstractThe aim of this study is to evaluate the protective effect of ethanol extract of Aerva lanata (EEAL) in preventing acetaminophen induced liver toxicity. EEAL was prepared and its hepatoprotective effect was studied in both isolated primary hepatocytes in vitro and in Sprague Dawley rats in vivo. For in vivo studies, the animals were grouped as Group I – Control; Group II – ACN (2 g/kg b.w.); Group III – EEAL (50 mg/kg b.w.) + ACN (2 g/kg b.w.), Group IV – EEAL (100 mg/kg b.w.) + ACN (2 g/kg b.w.). Extracellular activities of the enzymes liver aminotransferease (GOT, GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in isolated hepatocytes and rat plasma were studied colorimetrically. Expression of GST, Nrf2, COX 1 & COX2 genes in rat liver were evaluated by RT-PCR. The results showed that ACN induced down-regulation of Nrf2 and upregulation of GST gene expression, which were modulated by EEAL treatment. GOT, GPT, ALP and LDH levels were found to be lowered in both hepatocyte culture media and plasma following EEAL treatment. In addition, the medium GOT and GPT levels were diminished following EEAL treatment only. Moreover, only ALP and LDH in serum appeared to be at normal level following EEAL treatment, whereas GOT and GPT showed levels lower than control. ACN treatment increased the expression of pro-inflammatory COX 1 and COX 2 genes and the levels of these genes were reduced by EEAL treatment. EEAL pre-treated rats exposed to ACN were found to retain normal hepatic structure compared to ACN alone treated rats. From these results it can be concluded that ethanol extract of A. lanata possesses both anti-inflammatory and hepatoprotective activity.

Toxicogenomic Analysis of Cardiotoxicity in Rats

2008 ◽  
Vol 1 ◽  
pp. GEI.S851 ◽  
Author(s):  
Brad Hirakawa ◽  
Bart A. Jessen ◽  
Oscar Illanes ◽  
Ann de Peyster ◽  
Thomas McDermott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Carbon Tetrachloride ◽  
Rapid Assessment ◽  
Negative Control ◽  
Histopathological Analysis ◽  
Sprague Dawley ◽  
Post Dose ◽  
Sprague Dawley Rats ◽  
Control Compound

Evidence of cardiotoxicity in the preclinical testing of drugs will often lead to compound attrition. The standard method for identifying cardiotoxic compounds involves histopathological analysis of tissue sections, a resource intensive process. In an effort to reduce attrition and capture safety endpoints early within the drug discovery paradigm, a more rapid assessment of target organ effects is desired. Here we describe the results of a preliminary study in which a group of common genes were affected by in vivo exposure to compounds known to cause dose-dependant cardiotoxicity. Adult male Sprague-Dawley rats were treated intraperitoneally with a single dose of digoxin (20 mg/kg), doxorubicin (30 mg/kg), isoproterenol (70 mg/kg), lipopolysaccharide (10 mg/kg) or carbon tetrachloride (800 mg/kg) and euthanized either 6 or 24 hours post-dose. Digoxin, doxorubicin, isoproterenol, and lipopolysaccharide were chosen for this study based on their diverse mechanisms of cardiotoxicity. Carbon tetrachloride, a known liver toxicant, was chosen as a non-cardiotoxic negative control. Genes commonly affected by all four cardiotoxic compounds were grouped together as a list of potential biomarkers. Gene expression changes were subsequently quantified using quantitative PCR. These genes were compared to those affected by novel experimental compounds previously shown to cause cardiotoxicity in rats. These compounds also affected over half of the genes on the biomarker list, whereas the non-cardiotoxic control compound did not affect any genes on the biomarkers list. These data indicate that measuring changes in gene expression could aid in the prioritization of compounds before they are tested in more resource intensive studies.

scholarly journals Controlling gene expression with light: a multidisciplinary endeavour

2020 ◽  
Vol 48 (4) ◽  
pp. 1645-1659
Author(s):  
Denis Hartmann ◽  
Jefferson M. Smith ◽  
Giacomo Mazzotti ◽  
Razia Chowdhry ◽  
Michael J. Booth
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Cellular Damage ◽  
Biological Processes ◽  
Tissue Penetration ◽  
Spatiotemporal Resolution ◽  
Control Gene Expression ◽  
Diverse Field ◽  
Biological Methods

The expression of a gene to a protein is one of the most vital biological processes. The use of light to control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety of methods have been developed that use light to control the steps of transcription and translation of specific genes into proteins, for cell-free to in vivo biotechnology applications. These methods employ techniques ranging from the modification of small molecules, nucleic acids and proteins with photocages, to the engineering of proteins involved in gene expression using naturally light-sensitive proteins. Although the majority of currently available technologies employ ultraviolet light, there has been a recent increase in the use of functionalities that work at longer wavelengths of light, to minimise cellular damage and increase tissue penetration. Here, we discuss the different chemical and biological methods employed to control gene expression, while also highlighting the central themes and the most exciting applications within this diverse field.

Abstract P107: Anti- Mir-510 In The Treatment Of Essential Hypertension By Using Hypertensive Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Auxzilia Preethi K ◽  
Sushmaa Chandralekha J.S ◽  
Durairaj sekar
Keyword(s):  
Gene Expression ◽  
Rat Model ◽  
Luciferase Assay ◽  
Sprague Dawley ◽  
Critical Pathways ◽  
Cardiac Tissues ◽  
In Vivo Experiments ◽  
Huvec Cells

Introduction: Hypertension (HTN) is one of the major public health complications throughout the world. Although progress has been made in HTN research, early diagnosis and treatment of HTN are yet to be flourished. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in many diseases including HTN. According to our previous report, there is direct evidence showing that miR-510 is involved in HTN. Hypothesis: We assessed the hypothesis that to decipher the critical pathways of miR-510 and PTEN in regulation of PI3K/AKT Pathways, so it can be used as a therapeutic pathway as well as biomarker. Finally, we intend to study how anti-miR-510 reduces the HTN in the hypertensive induced rat model. Methodology: Proliferation, migration, invasion and apoptosis capacity of miR-510, Anti-miR-510, PTEN and eNOS were evaluated in HUVEC Cells. The expression pattern of miR-510, anti-miR-510 and eNOS, PTEN are analyzed by qPCR and western blot The relationship between miR-510, Anti-miR-510 and PTEN are investigated by luciferase assay Deoxycorticosterone acetate (DOCA) of 70mg/kg and 1% NaCl salt induced hypertension model (Sprague Dawley rats) was used in this study. According to the dose dependent study, anti-miR-510 was administered intravenously. Histological analyses are performed to examine the hypertrophy by using cardiac tissues fixed in 1% paraformaldehyde. Results and conclusion: Our results suggested that miR-510 can directly influence the PTEN expressions in HUVEC cells. Furthermore, the in vitro experiments clearly indicated that miR-510/PI3K/AKT/PTEN axis involved in HTN. Anti-miR-510 delivery can reduce the progression of HTN in the hypertensive induced rat model. Though miR-510 is involved in HTN, but its molecular mechanism is almost unknown. So, these analyses suggested that the correlation between miR-510, PTEN, anti-miR-510 are the critical step in gene expression and regulations. Thus, all these analyses could lead in identification of therapeutic target and non-invasive biomarker for HTN. Our in vivo experiments suggesting that anti-miR-510 may act as a novel therapeutic molecule for HTN treatment.

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