scholarly journals Astragalus Extract Mixture HT042 Increases Longitudinal Bone Growth Rate by Upregulating Circulatory IGF-1 in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Donghun Lee ◽  
Sung Hyun Lee ◽  
Yoon Hee Lee ◽  
Jungbin Song ◽  
Hocheol Kim
Keyword(s):  
Growth Rate ◽  
Protein Expression ◽  
Growth Plate ◽  
Bone Growth ◽  
Height Growth ◽  
Normal Functioning ◽  
Direct Stimulation ◽  
Proliferative Rate ◽  
Stimulation Of ◽  
Igfbp 3

Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of “height growth of children.” HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration. HT042 upregulated liver IGF-1 and IGFBP-3 mRNA expression, IGF-1 protein expression, and phosphorylation of JAK2/STAT5. HT042 also increased bone growth rate and proliferative zonal height in growth plate. In conclusion, HT042 stimulates bone growth rate via increment of proliferative rate by upregulation of liver IGF-1 and IGFBP-3 mRNA followed by IGF-1 protein expression through phosphorylation of JAK2/STAT5, which can be regarded as normal functioning of GH-dependent endocrine pathway.

scholarly journals Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1820-1828 ◽  
Author(s):  
Rose Marino ◽  
Anita Hegde ◽  
Kevin M. Barnes ◽  
Lenneke Schrier ◽  
Joyce A. Emons ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Inhibition ◽  
Growth Plate ◽  
Bone Growth ◽  
Structural Characteristics ◽  
Linear Growth Rate ◽  
Growth Plate Chondrocytes ◽  
Growth Plates ◽  
Catch Up ◽  
Growth Inhibiting

Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.

scholarly journals Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model

2019 ◽  
Vol 20 (20) ◽  
pp. 5198
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Growth Plate ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Long Bone ◽  
Tunel Staining ◽  
Long Bones ◽  
Micro Computed Tomography ◽  
Calcified Tissue ◽  
Trap Staining ◽  
Stimulation Of

Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. RXR agonist-treated rats had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence with p57 immunostaining. Additionally, SOX9-positive cells were found surrounding the calcified tissue. The epiphysis of SR11237-treated bones showed increased TRAP staining and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of the treated animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models

scholarly journals A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2625
Author(s):  
Ok-Kyung Kim ◽  
Jeong moon Yun ◽  
Minhee Lee ◽  
Soo-Jeung Park ◽  
Dakyung Kim ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Tail Length ◽  
Janus Kinase ◽  
Sprague Dawley ◽  
Plate Height ◽  
Longitudinal Bone Growth ◽  
Sd Rats ◽  
Humulus Japonicus ◽  
Igfbp 3

The aim of this study was to investigate the effects of administration of a mixture of Humulus japonicus (MH) on longitudinal bone growth in normal Sprague Dawley (SD) rats. We measured the femur and tibia length, growth plate area, proliferation of chondrocytes, and expression of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3), and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) phosphorylation after dietary administration of MH in SD rats for four weeks. The nose–tail length gain and length of femur and tibia increased significantly in the group that received MH for a period of four weeks. We performed H&E staining and Bromodeoxyuridine/5-Bromo-2′-Deoxyuridine (BrdU) staining to examine the effect of dietary administration of MH on the growth plate and the proliferation of chondrocytes and found that MH stimulated the proliferation of chondrocytes and contributed to increased growth plate height during the process of longitudinal bone growth. In addition, serum levels of IGF-1 and IGFBP-3 and expression of IGF-1 and IGFBP-3 mRNAs in the liver and bone were increased, and phosphorylation of JAK2/STAT5 in the liver was increased in the MH groups. Based on these results, we suggest that the effect of MH on longitudinal bone growth is mediated by increased JAK2/STAT5-induced IGF-1 production.

scholarly journals Effects of Laser Acupuncture on Longitudinal Bone Growth in Adolescent Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Mijung Yeom ◽  
Sung-Hun Kim ◽  
Bina Lee ◽  
Xiuyu Zhang ◽  
Hyangsook Lee ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Plate ◽  
Bone Growth ◽  
Growth Potential ◽  
Male Rats ◽  
Adolescent Male ◽  
Laser Acupuncture ◽  
Longitudinal Bone Growth ◽  
Level Laser ◽  
Adolescent Rats

Longitudinal bone growth is the results of chondrocyte proliferation and hypertrophy and subsequent endochondral ossification in the growth plate. Recently, laser acupuncture (LA), an intervention to stimulate acupoint with low-level laser irradiation, has been suggested as an intervention to improve the longitudinal bone growth. This study investigated the effects of laser acupuncture on growth, particularly longitudinal bone growth in adolescent male rats. Laser acupuncture was performed once every other day for a total of 9 treatments over 18 days to adolescent male rats. Morphometry of the growth plate, longitudinal bone growth rate, and the protein expression of BMP-2 and IGF-1 in growth plate were observed. The bone growth rate and the heights of growth plates were significantly increased by laser acupuncture. BMP-2 but not IGF-1 immunostaining in growth plate was increased as well. In conclusion, LA promotes longitudinal bone growth in adolescent rats, suggesting that laser acupuncture may be a promising intervention for improving the growth potential for children and adolescents.

Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits

1992 ◽  
Vol 263 (3) ◽  
pp. E489-E492 ◽  
Author(s):  
J. Baron ◽  
Z. Huang ◽  
K. E. Oerter ◽  
J. D. Bacher ◽  
G. B. Cutler
Keyword(s):  
Growth Rate ◽  
Growth Plate ◽  
Bone Growth ◽  
Potent Inhibitor ◽  
Local Effects ◽  
Inhibition Of Growth ◽  
Potent Inhibition ◽  
Dexamethasone Phosphate ◽  
Tibial Growth Plate

Excess glucocorticoid is a potent inhibitor of epiphysial growth. Several mechanisms have been suggested to explain this growth inhibition, including both direct local effects of glucocorticoid on the epiphysial growth plate and indirect systemic effects. Previous studies do not distinguish which of these proposed mechanisms is actually responsible for the growth suppression in vivo. To resolve this controversy, we developed a method for delivering glucocorticoid directly into the rabbit epiphysial growth plate and for accurately measuring the resulting epiphysial growth rate. Five-week-old male rabbits received a local infusion of dexamethasone phosphate (80 ng/microliters, 1 microliters/h) into one proximal tibial growth plate and an infusion of vehicle into the contralateral growth plate. Growth rate was determined by inserting metal pins into the bone immediately adjacent to the growth plate and measuring the change in distance between pins on serial radiographs. This method permitted growth rates to be measured over intervals as short as 3 days, with an error of approximately 5%. Local dexamethasone administration decreased proximal tibial growth rate by 77% compared with the contralateral vehicle-treated tibia (P less than 0.0001). We conclude that excess glucocorticoid causes a rapid potent inhibition of growth by a direct local action on the growth plate.

scholarly journals Alendronate Inhibits VEGF Expression in Growth Plate Chondrocytes by Acting on the Mevalonate Pathway

2009 ◽  
Vol 3 (1) ◽  
pp. 83-88 ◽  
Author(s):  
K.D. Evans ◽  
A.M. Oberbauer
Keyword(s):  
Protein Expression ◽  
Growth Plate ◽  
Intracellular Signaling ◽  
Bone Growth ◽  
Mevalonate Pathway ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Growth Plate Chondrocytes ◽  
Mrna Isoforms ◽  
Vegf Protein

Bisphosphonates decrease chondrocyte turnover at the growth plate and impact bone growth. Likewise vascular endothelial growth factor (VEGF) plays an important role in endochondral bone elongation by influencing chondrocyte turnover at the growth plate. To investigate whether the action of bisphosphonate on the growth plate works through VEGF, VEGF protein expression and isoform transcription in endochondral chondrocytes isolated from growing mice and treated with a clinically used bisphosphonate, alendronate, were assessed. Alendronate at 10µM and 100µM concentrations decreased secreted VEGF protein expression but not cell associated protein. Bisphosphonates are known to inhibit the mevalonate intracellular signaling pathway used by VEGF. Addition of the mevalonate pathway intermediates farnesol (FOH) and geranylgeraniol (GGOH) interacted with the low concentration of alendronate to further decrease secreted VEGF protein whereas FOH partially restored VEGF protein secretion when combined with the high alendronate. Similar to the protein data, the addition of alendronate decreased VEGF mRNA isoforms. VEGF mRNA levels were rescued by the GGOH mevalonate pathway intermediate at the low alendronate dose whereas neither intermediate consistently restored the VEGF mRNA levels at the high alendronate dose. Thus, the bisphophonate alendronate impairs growth plate chondrocyte turnover by down-regulating the secreted forms of VEGF mRNA and protein by inhibiting the mevalonate pathway.

Effects of Uranium (VI) Stress on Growth and Antioxidant System in Chinese Cabbage

2014 ◽  
Vol 887-888 ◽  
pp. 581-584 ◽  
Author(s):  
Lei Xie ◽  
Wen Ling Tang
Keyword(s):  
Growth Rate ◽  
Plant Height ◽  
Chlorophyll A ◽  
Chinese Cabbage ◽  
Root Elongation ◽  
Uranium Concentration ◽  
Height Growth ◽  
Excess Concentration ◽  
Physiological And Biochemical ◽  
Stimulation Of

Chinese cabbage plants exposed to different concentrations of Uranium in water culture were used to discuss the physiological and biochemical responses:the plant height growth rate,root elongation,superoxide dismutase (SOD),catalase (CAT),Peroxidase (POD),Chlorophyll a,Soluble protein.The results show that high Uranium stress can hinder the plants growth because the plant height growth rate and root elongation of the plants treated with high Uranium concentration were both lower than the control group.Exposure to excess concentration of Uranium decreased the content of chlorophyll a,soluble protein and the activity of SOD.The CAT activity was induced in the presence of 0.1mg/L uranium concentration and inhibited under higher uranium stress.While the stimulation of POD activity can indicate that it act as H2O2scavengers.

scholarly journals C-type natriuretic peptide improves growth retardation in a mouse model of cardio-facio-cutaneous syndrome

2018 ◽  
Vol 28 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Shin-ichi Inoue ◽  
Naomi Morozumi ◽  
Kazunori Yoshikiyo ◽  
Hiroaki Maeda ◽  
Yoko Aoki
Keyword(s):  
Growth Plate ◽  
Natriuretic Peptide ◽  
Growth Retardation ◽  
Bone Growth ◽  
Heart Defects ◽  
Genetic Disorder ◽  
Erk Activation ◽  
Cfc Syndrome ◽  
Plate Width ◽  
Igfbp 3

Abstract Cardio-facio-cutaneous (CFC) syndrome, a genetic disorder caused by germline mutations in BRAF, KRAS, MAP2K1 and MAP2K2, is characterized by growth retardation, heart defects, dysmorphic facial appearance and dermatologic abnormalities. We have previously reported that knock-in mice expressing the CFC syndrome-associated mutation, Braf Q241R, showed growth retardation because of gastrointestinal dysfunction. However, other factors associated with growth retardation, including chondrogenesis and endocrinological profile, have not been examined. Here, we show that 3- and 4-week-old BrafQ241R/+ mice have decreased body weight and length, as well as reduced growth plate width in the proximal tibiae. Furthermore, proliferative and hypertrophic chondrocyte zones of the growth plate were reduced in BrafQ241R/+ mice compared with Braf+/+ mice. Immunohistological analysis revealed that extracellular signal-regulated kinase (ERK) activation was enhanced in hypertrophic chondrocytes in BrafQ241R/+ mice. In accordance with growth retardation and reduced growth plate width, decreased serum levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) were observed in BrafQ241R/+ mice at 3 and 4 weeks of age. Treatment with C-type natriuretic peptide (CNP), a stimulator of endochondral bone growth and a potent inhibitor of the FGFR3-RAF1-MEK/ERK signaling, increased body and tail lengths in Braf+/+ and BrafQ241R/+ mice. In conclusion, ERK activation in chondrocytes and low serum IGF-1/IGFBP-3 levels could be associated with the growth retardation observed in BrafQ241R/+ mice. Our data also suggest that CNP is a potential therapeutic target in CFC syndrome.

Analysis of Association between Morphometric Parameters of Growth Plate and Bone Growth of Tibia in Mice and Humans

Cartilage ◽  
2020 ◽  
pp. 194760351990080 ◽  
Author(s):  
Kimberly Wilson ◽  
Yu Usami ◽  
Danielle Hogarth ◽  
Amanda L. Scheiber ◽  
Hongying Tian ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Plate ◽  
Linear Correlation ◽  
Bone Growth ◽  
Plate Height ◽  
Total Height ◽  
Tibia Bone ◽  
Proliferation Activity ◽  
Tibia Length ◽  
Plate Width

Objective The purposes of this study are to evaluate which growth plate parameters are associated with bone growth in mice and to compare the mouse results with those in humans. Design The sagittal sections of the proximal growth plate of the mouse tibia from neonate to young adult stages were subjected to histomorphometric and functional analyses. The radiographic images of tibias of human patients until puberty were analyzed to obtain the tibia length and the proximal growth plate height. It was found that a linear correlation best modeled the relationship between the growth plate variables with the tibia growth rate and length. Results In mice, total height, resting zone height, combined height of the proliferation and prehypertrophic zones, proliferation activity, and the total width of tibia growth plate showed high linear correlation with tibia bone length and bone growth rate, but the hypertrophic zone height and the growth plate area did not. In both mice and humans, the total growth plate width of tibia was found to have the strongest correlation with tibia length and growth rate. Conclusions The results validated that growth plate total height, the height of the resting zone and cell proliferation activity are appropriate parameters to evaluate the balance between growth plate activity and bone growth in mice, consistent with previous reports. The study also provided a new growth plate parameter candidate, growth plate width for growth plate activity evaluation in both mouse and human tibia bone.

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