scholarly journals Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency

2018 ◽  
Vol 237 (3) ◽  
pp. 229-242 ◽  
Author(s):  
Majdi Masarwi ◽  
Raanan Shamir ◽  
Moshe Phillip ◽  
Galia Gat-Yablonski
Keyword(s):  
Short Stature ◽  
Growth Plate ◽  
Treatment Strategies ◽  
Young Male ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Epiphyseal Growth Plate ◽  
Catch Up

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90–120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children.

Involvement of matrix metalloproteinases in the growth plate response to physiological mechanical load

2010 ◽  
Vol 108 (1) ◽  
pp. 172-180 ◽  
Author(s):  
Adi Reich ◽  
Stav Simsa Maziel ◽  
Ziv Ashkenazi ◽  
Efrat Monsonego Ornan
Keyword(s):  
Growth Plate ◽  
Mechanical Loading ◽  
Mechanical Load ◽  
Tissue Growth ◽  
Matrix Assembly ◽  
Growth Plates ◽  
Load Release ◽  
Catch Up

Enzymes from the matrix metalloproteinase (MMP) family play a crucial role in growth-plate vascularization and ossification via proteolytic cleavage and remodeling of the extracellular matrix. Their regulation in the growth plate is crucial for normal matrix assembly. Endochondral ossification, which takes place at the growth plates, is influenced by mechanical loading. Using an in vivo avian model for mechanical loading, we have found increased blood penetration into the growth plates of loaded chicks. The purpose of this work was to study the involvement of MMP-2, -3, -9, -13, and -16 in the growth plate's response to loading and in the catch-up growth resulting from load release. We found that mechanical loading, as well as release from load, upregulated MMP-2, -9, and -13 expressions. In contrast, MMP-3, associated with cartilage injuries, and its associated protein connective tissue growth factor (CTGF), were downregulated by the load. However, after release from load, MMP-3 was upregulated and CTGF levels were elevated and caught up with the control. MMP-3 and CTGF were also downregulated after 60 min of mechanical stretching in vitro. These results demonstrate the central role of MMPs in the growth plate's response to mechanical loading, as well as in the catch-up growth followed load release.

scholarly journals Inhibitory Effects of Raw-Extract Centella asiatica (RECA) on Acetylcholinesterase, Inflammations, and Oxidative Stress Activities via In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 892 ◽  
Author(s):  
Zetty Zulikha Hafiz ◽  
Muhammad ‘Afif Mohd Amin ◽  
Richard Muhammad Johari James ◽  
Lay Kek Teh ◽  
Mohd Zaki Salleh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Centella Asiatica ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Sprague Dawley Rats ◽  
And Oxidative Stress

Centella asiatica (C. asiatica) is one of the medicinal plants that has been reported to exert comprehensive neuroprotection in vitro and in vivo. In view of this, the present study was performed to investigate the effect of ethanolic extract of C. asiatica, designated as raw-extract of C. asiatica (RECA) in reducing the acetylcholinesterase (AChE), inflammations, and oxidative stress activities via both in vitro (SH-SY5Y and RAW 264.7 cells) and in vivo (Sprague Dawley rats). Quantitative high-performance liquid chromatography analysis reveals that RECA contains a significantly high proportion of glycosides than the aglycones with madecassoside as the highest component, followed by asiaticoside. Treatment of SH-SY5Y cells with RECA significantly reduced the AChE activity in a concentration-dependent manner with an IC50 value of 31.09 ± 10.07 µg/mL. Furthermore, the anti-inflammatory and antioxidant effects of RECA were evaluated by lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. Our results elucidated that treatment with RECA significantly suppressed the level of pro-inflammatory cytokine/mediators and oxidative stress released in a concentration-dependent manner. Interestingly, these patterns of inhibition were consistent as observed in the LPS-induced neuroinflammation Sprague Dawley rats’ model. The highest concentration used in the two models presented the most significant results. Herein, our findings strongly suggest that RECA may offer therapeutic potential for the treatment of Alzheimer’s disease through inhibiting the AChE, inflammation, and oxidative stress activities.

scholarly journals Aqueous Extract of Perilla frutescens var. acuta Relaxes the Ciliary Smooth Muscle by Increasing NO/cGMP Content In Vitro and In Vivo

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1777 ◽  
Author(s):  
Jaeyong Kim ◽  
Huwon Kang ◽  
Hakjoon Choi ◽  
Ara Jo ◽  
Dooi-Ri Oh ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Perilla Frutescens ◽  
Ciliary Muscle ◽  
Control Group ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Eye Fatigue ◽  
Freeze Dried

The leaves of Perilla frutescens var. acuta (PFA) are commonly used as a traditional medicine in Korea, Japan, and China. We previously showed that PFA attenuates eye fatigue by improving visual accommodation through a clinical study. However, detailed mechanisms and chemical compounds have not been studied. In this study, we analyzed the active compounds in an aqueous extract of PFA involved in ciliary muscle relaxation in vitro and in vivo. NMR and MS analyses showed that the PFA extract contained mainly luteolin-7-O-diglucuronide and apigenin-7-O-diglucuronide. The composition after freeze-drying and spray-drying was similar. Freeze-dried PFA (50 µg/mL, 100 µg/mL, and 200 µg/mL) increased nitric oxide and cGMP levels in ciliary muscle cells isolated from the eyes of rats. [Ca2+]i decreased in a dose-dependent manner. Furthermore, Sprague-Dawley rats treated with freeze-dried PFA (200 mg/kg, orally) showed significantly increased cGMP levels compared with the control group and irradiated with white light. Our results suggest that PFA extract has the potential to reduce eye fatigue by relaxing ciliary muscles.

scholarly journals Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague–Dawley rats

2016 ◽  
Vol 116 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Majdi Masarwi ◽  
Yankel Gabet ◽  
Oleg Dolkart ◽  
Tamar Brosh ◽  
Raanan Shamir ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Quality ◽  
Young Male ◽  
Growth Potential ◽  
Male Rats ◽  
Sprague Dawley ◽  
Epiphyseal Growth Plate ◽  
Sprague Dawley Rats ◽  
Catch Up

AbstractThe aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague–Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins – casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth.

Identification of aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) as novel renal damage biomarkers following exposure to mercury

2018 ◽  
Vol 37 (10) ◽  
pp. 1025-1036 ◽  
Author(s):  
Y-J Shin ◽  
K-A Kim ◽  
E-S Kim ◽  
J-H Kim ◽  
H-S Kim ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Dependent Manner ◽  
Clinical Markers ◽  
Sprague Dawley ◽  
Glutathione S Transferase ◽  
Protein Levels ◽  
Kidney Proximal Tubular Cells ◽  
New Biomarkers

The kidney is one of the main targets for toxicity induced by xenobiotics. Sensitive detection of early impairment is critical to assess chemical-associated renal toxicity. The aim of this study was to identify potential nephrotoxic biomarkers in rat kidney tissues after exposure to mercury (Hg), a representative nephrotoxicant, and to evaluate these new biomarkers employing in vivo and in vitro systems. Mercuric chloride was administered orally to Sprague-Dawley rats for 2 weeks. Proteomic analysis revealed that aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) were significantly elevated in kidney after Hg exposure. While the levels of conventional nephrotoxic clinical markers including blood urea nitrogen and serum creatinine were not elevated, the mRNA and protein levels of AKR7A1 and GSTP1 were increased upon Hg exposure in a dose-dependent manner. The increases in AKR7A1 and GSTP1 were also observed in rat kidneys after an extended exposure for 6 weeks to low-dose Hg. In in vitro rat kidney proximal tubular cells, changes in AKR7A1 and GSTP1 levels correlated well with the extent of cytotoxicity induced by Hg, cadmium, or cisplatin. AKR7A1 and GSTP1 were identified as new candidates for Hg-induced nephrotoxicity, suggesting that these biomarkers have potential for evaluating or predicting nephrotoxicity.

A study of the chemical binding of allyl isothiocyanate with thyroxine and of the effect of allyl isothiocyanate on lipid metabolism in the rat

1979 ◽  
Vol 57 (4) ◽  
pp. 385-389 ◽  
Author(s):  
A. Jabbar Muztar ◽  
Parvez Ahmad ◽  
Taufiqul Huque ◽  
S. J. Slinger
Keyword(s):  
Liver Lipid ◽  
Lipid Production ◽  
Young Male ◽  
Allyl Isothiocyanate ◽  
Liver Protein ◽  
Sprague Dawley ◽  
Chemical Binding ◽  
Lipid Contents

Two experiments were conducted with allyl isothiocyanate (AITC): one in vitro, to investigate the chemical binding of AITC with thyroxine (T4), tyrosine (Tyr), and leucine (Leu), and the other in vivo, to evaluate the effect of AITC on the blood clotting mechanism and on the protein and lipid contents of rat liver. The in vitro study, which used the techniques of ultraviolet spectroscopy and thin-layer chromatography, indicated the formation of a complex of AITC with T4 and Tyr but not with Leu. The presence of a phenyl ring with an OH group at the position para to the alanine side chain is suggested as a prerequisite for the chemical binding of AITC with amino acids. The in vivo experiment involved administration of AITC, T4, or the ALTC–T4 complex by the intraperitoneal route to young male Sprague–Dawley rats for 30 days. AITC exhibited a strong coagulant effect, which was seemingly mediated by the relatively high plasma phospholipid concentration. T4 and the AITC–T4 complex were without a significant effect on blood coagulation. AITC was without effect on liver protein but increased cholesterol, phospholipid, and total lipid contents markedly. The effect of T4 on the liver protein and lipids was not significant. The AITC-T4 complex caused a significant increase in the liver protein and an intermediate rise in the lipids compared with AITC. The increase in plasma and liver lipid concentrations caused by AITC was probably related to increased hepatic lipid production and decreased clearance of the circulating lipids.

scholarly journals Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-11
Author(s):  
Chihiro Ito ◽  
Yoshiki Mukudai ◽  
Masakatsu Itose ◽  
Kosuke Kato ◽  
Hiromi Motohashi ◽  
...  
Keyword(s):  
Terminal Differentiation ◽  
Dependent Manner ◽  
Epiphyseal Growth Plate ◽  
Knock Down ◽  
Normal Tissues ◽  
Proliferation And Differentiation ◽  
First Time ◽  
Tumor Proteins

The tumor protein D (TPD) family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate. In MC3T3E-1 cells, the expressions of TPD52 and TPD54 were increased in a differentiation-dependent manner. In contrast, their expressions were decreased in ATDC5 cells. In ATDC5 cells, overexpression of TPD52 decreased alkaline phosphatase (ALPase) activity, while knock-down of TPD52 showed little effect. In contrast, overexpression of TPD54 enhanced ALPase activity, Ca2+ deposition, and the expressions of type X collagen and ALPase genes, while knock-down of TPD54 reduced them. The results revealed that TPD52 inhibits and that TPD54 promotes the terminal differentiation of a chondrocyte cell line. As such, we report for the first time the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification.

scholarly journals Nontoxic Glucomoringin-Isothiocyanate (GMG-ITC) Rich Soluble Extract Induces Apoptosis and Inhibits Proliferation of Human Prostate Adenocarcinoma Cells (PC-3)

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1174 ◽  
Author(s):  
Mohammed Jaafaru ◽  
Nurul Abd Karim ◽  
Enas Mohamed Eliaser ◽  
Peter Maitalata Waziri ◽  
Hamidu Ahmed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acute Toxicity ◽  
Prostate Adenocarcinoma ◽  
Human Prostate ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Adenocarcinoma Cells

The incidence of prostate cancer malignancy along with other cancer types is increasing worldwide, resulting in high mortality rate due to lack of effective medications. Moringa oleifera has been used for the treatment of communicable and non-communicable ailments across tropical countries, yet, little has been documented regarding its effect on prostate cancer. We evaluated the acute toxicity and apoptosis inducing effect of glucomoringin-isothiocyanate rich soluble extracts (GMG-ITC-RSE) from M. oleifera in vivo and in vitro, respectively. Glucomoringin was isolated, identified, and characterized using fundamental analytical chemistry tools where Sprague-Dawley (SD) rats, murine fibroblast (3T3), and human prostate adenocarcinoma cells (PC-3) were used for acute toxicity and bioassays experiments. GMG-ITC-RSE did not instigate adverse toxic reactions to the animals even at high doses (2000 mg/kg body weight) and affected none of the vital organs in the rats. The extract exhibited high levels of safety in 3T3 cells, where more than 90% of the cells appeared viable when treated with the extract in a time-dependent manner even at high dose (250 µg/mL). GMG-ITC-RSE significantly triggered morphological aberrations distinctive to apoptosis observed under microscope. These findings obviously revealed the putative safety of GMG-ITC-RSE in vivo and in vitro, in addition to its anti-proliferative effect on PC-3 cells.

INFLUENCE OF OXYGEN TENSION ON SOMATOMEDIN ACTIVITY IN VITRO

1977 ◽  
Vol 72 (3) ◽  
pp. 361-369 ◽  
Author(s):  
JENNIFER M. DEHNEL ◽  
D. L. HAMBLEN
Keyword(s):  
Growth Plate ◽  
Oxygen Tension ◽  
Atmospheric Oxygen ◽  
Calf Serum ◽  
Growth Patterns ◽  
Foetal Calf Serum ◽  
Low Oxygen ◽  
Epiphyseal Growth Plate

SUMMARY Somatomedins are the intermediaries through which growth hormone acts on the epiphyseal growth plate to effect linear skeletal growth. Rat epiphyseal chondrocytes were isolated and cultured in vitro in the presence of somatomedin. Two sources of somatomedin were used, foetal calf serum and rat liver perfusates. The chondrocytes proliferated and synthesized sulphated glycosaminoglycans when grown in the presence of somatomedin from either source, but were not metabolically active in chemically defined medium alone. Some differences in the growth patterns in response to serum or liver somatomedins are reported and discussed. Chondrocyte metabolic activity in the presence of somatomedin in vitro showed a graded response to alterations in the atmospheric oxygen, being greatest at low oxygen pressure, and almost completely inhibited at 95% oxygen. A gradient of local oxygen tension has been reported to exist across the epiphyseal plate in vivo. The effects of somatomedin combined with changing oxygen levels may help to explain the divergence of cell proliferation and matrix synthesis seen in the various regions of the growth plate.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

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