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.

scholarly journals Effect of Pulsed Electromagnetic Field Stimulation on the Growth Plate of the Tibia Bone of Rats: An In Vivo Study

2021 ◽  
Vol 11 (16) ◽  
pp. 7571
Author(s):  
Yoon-Young Sung ◽  
Jae-Woo Shin ◽  
Won-Kyung Yang ◽  
Min-Jin Kim ◽  
Ja-Ik Koo ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Growth Plate ◽  
Bone Growth ◽  
Articular Chondrocytes ◽  
Growth Promotion ◽  
Control Group ◽  
Pulsed Electromagnetic Field ◽  
Tibia Bone ◽  
Pulsed Electromagnetic

Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. Pulsed electromagnetic field (PEMF) stimulation induces cell proliferation of articular chondrocytes. We developed a method for growth promotion using equipment with PEMF. In this study, we aimed to evaluate the effects of PEMF on the growth rate of growth plates using an animal model. An experimental study was conducted on 16 3-week-old rats to validate the effects of the growth care device on growth and development by PEMF stimulation at 28 Hz and 20 Gauss. The tibia bones of the groups with and without PEMF administration were dissected after 10 days, and then, the length of the growth plate of the knee and levels of insulin-like growth factor (IGF)-1 hormone in serum were measured. The length of the growth plate on the tibia bone and the levels of circulating IGF-1 were significantly increased by 25.6% and 13.6%, respectively, in the experimental group to which PEMF was applied compared to those of the control group, without any side effects. These results suggest that PEMF can safely stimulate growth of the growth plate in a non-invasive manner to promote bone growth.

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 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 BONE GROWTH AND DISTRIBUTION IN SWINE AS INFLUENCED BY LIVEWEIGHT, BREED, SEX, AND RATION

1972 ◽  
Vol 52 (1) ◽  
pp. 47-56 ◽  
Author(s):  
R. J. RICHMOND ◽  
R. T. BERG
Keyword(s):  
Growth Rate ◽  
Bone Growth ◽  
Skeletal Development ◽  
Lumbar Vertebrae ◽  
High Energy ◽  
Low Energy ◽  
Thoracic Vertebrae ◽  
Yorkshire Pigs ◽  
Tibia Length ◽  
Anterior Posterior

Individual bones of the skeleton, dissected from one-half of the carcass were weighed and expressed as a percentage of total bone for 23 Duroc × Yorkshire, 42 Hampshire × Yorkshire, and 27 Yorkshire × Yorkshire barrows and gilts fed either low energy (LE) (2757 kcal DE/kg and 15.3% protein) or high energy (HE) (3652 kcal DE/kg and 19.9% protein) rations and slaughtered at either 68, 91, or 114 kg liveweight. To determine bone measurements at the start of the experiment bone data were collected from seven barrows and seven gilts of the same breed groups slaughtered at 23 kg liveweight. The scapula, humerus, radius, and ulna, femur, and tibia bones, in addition to being weighed, were measured to determine length and circumference. Increases in bone length were proportionate to liveweight up to 91 kg, after which growth rate decreased for all measured bones except the humerus. Growth in circumference increased rapidly for all measured bones up to 68 kg liveweight, after which increases were of lesser magnitude. Between 23 and 68 kg liveweight, increases in bone circumference were slightly greater than those in length. Weight for each measured bone increased linearily relative to liveweight. Among breed groups Duroc × Yorkshire pigs had the greatest radius and ulna circumference and Hampshire × Yorkshire the smallest tibia weight (P < 0.05). Gilts had a greater scapula length and weight and a greater femur and tibia length than did barrows (P < 0.05). Pigs fed the low energy ration exceeded those fed the high energy ration in scapula length (19.67 vs. 19.08 cm) and weight (171.52 vs. 157.25 g). Sex-liveweight and sex-ration interactions occurred for femur weight and percent scapula, respectively. Percentage bone in the carcass decreased as liveweight increased but percent bone within the hind and front quarters remained relatively constant after 68 kg liveweight. The influence of breed, sex, and ration on percentages of individual bones were observed only for the scapula, radius, and ulna and sternum and rib cartilage. A decrease in percent thoracic vertebrae and increase in percent ribs and lumbar vertebrae indicated an anterior-posterior pattern of skeletal development. Differentiation in bone distribution appeared to be essentially complete at or before 23 kg liveweight.

Direct administration of testosterone increases rat tibial epiphyseal growth plate width

1989 ◽  
Vol 121 (3) ◽  
pp. 401-405 ◽  
Author(s):  
Song Guang Ren ◽  
Saul Malozowski ◽  
Prosper Sanchez ◽  
Donald E. Sweet ◽  
D. Lynn Loriaux ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Serum Testosterone ◽  
Male Rats ◽  
Testosterone Enanthate ◽  
Epiphyseal Growth Plate ◽  
Igf I ◽  
Direct Administration ◽  
Tibial Epiphyseal ◽  
Plate Width

Abstract. Local injection of hormones into the tibial epiphyseal growth plate offers a possible model to answer whether sex steroids can affect bone growth directly. To answer this question, we injected different doses of testosterone enanthate (4, 40, 120 and 400 μg/100 g of rat weight) once into the tibial epiphyseal growth plate of castrated 35-day-old male rats. The contralateral tibia was injected with sesame oil and served as control. All animals were sacrificed at age 42 days. Tibias were removed for measurement of epiphyseal growth plate width and blood was collected for measurement of serum IGF-I and testosterone. The lower doses of testosterone enanthate (4, 40 and 120 μg/100 g) did not produce any significant change in epiphyseal growth plate width. Testosterone at the largest dose tested (400 μg/100 g) increased epiphyseal growth plate width by about 15% compared to control (p < 0.01). At this dose, serum testosterone was not increased, suggesting that the effect on epiphyseal growth plate width was not due to higher systemic testosterone concentrations. No differences in IGF-I levels were observed among the groups. We conclude that direct administration of testosterone enanthate at a dose of 400 μg/100 g into the rat tibial epiphyseal growth plate can increase epiphyseal growth plate width.

scholarly journals The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

2012 ◽  
Vol 302 (11) ◽  
pp. E1381-E1389 ◽  
Author(s):  
A. E. Börjesson ◽  
S. H. Windahl ◽  
E. Karimian ◽  
E. E. Eriksson ◽  
M. K. Lagerquist ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
High Dose ◽  
Plate Height ◽  
Chondrocyte Proliferation ◽  
Growth Plates ◽  
Longitudinal Bone Growth ◽  
Female Mice

High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-α stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ERα and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERα (ERα−/−) or ERαAF-1 (ERαAF-10) were evaluated. Old (16- to 19-mo-old) female ERα−/− mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ERαAF-10 mice (tibia: −4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERαAF-10 mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ERα−/− mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ERα or aromatase. In contrast, ERαAF-1 deletion results in a hyperactive ERα, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERα that do not require AF-1 and that ERαAF-1 opposes growth plate closure.

scholarly journals Evidence That Estrogen Hastens Epiphyseal Fusion and Cessation of Longitudinal Bone Growth by Irreversibly Depleting the Number of Resting Zone Progenitor Cells in Female Rabbits

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2892-2899 ◽  
Author(s):  
Ola Nilsson ◽  
Martina Weise ◽  
Ellie B.M. Landman ◽  
Jodi L. Meyers ◽  
Kevin M. Barnes ◽  
...  
Keyword(s):  
Growth Rate ◽  
Progenitor Cells ◽  
Cell Size ◽  
Growth Plate ◽  
Structural Parameters ◽  
Proliferation Rate ◽  
Estrogen Treatment ◽  
Plate Height ◽  
Hypertrophic Cell ◽  
Epiphyseal Fusion

With age, growth plate cartilage undergoes programmed senescence, eventually causing cessation of bone elongation and epiphyseal fusion. Estrogen accelerates this developmental process. We hypothesized that senescence occurs because progenitor cells in the resting zone are depleted in number and that estrogen acts by accelerating this depletion. To test this hypothesis, juvenile ovariectomized rabbits received injections of estradiol cypionate or vehicle for 5 weeks, and then were left untreated for an additional 5 weeks. Exposure to estrogen accelerated the normal decline in growth plate height and in the number of proliferative and hypertrophic chondrocytes. Five weeks after discontinuation of estrogen treatment, these structural parameters remained advanced, indicating an irreversible advancement in structural senescence. Similarly, transient estrogen exposure hastened epiphyseal fusion. Estrogen also caused a more rapid decline in functional parameters of growth plate senescence, including growth rate, proliferation rate, and hypertrophic cell size. However, in contrast to the structural parameters, once the estrogen treatment was discontinued, the growth rate, chondrocyte proliferation rate, and hypertrophic cell size all normalized, suggesting that estrogen has a reversible, suppressive effect on growth plate function. In addition, estrogen accelerated the normal loss of resting zone chondrocytes with age. This decrease in resting zone cell number did not appear to be due to apoptosis. However, it was maintained after the estrogen treatment stopped, suggesting that it represents irreversible depletion. The findings are consistent with the hypothesis that estrogen causes irreversible depletion of progenitor cells in the resting zone, thus irreversibly accelerating structural senescence and hastening epiphyseal fusion. In addition, estrogen reversibly suppresses growth plate function.

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 Regulation of bone growth via ligand-specific activation of estrogen receptor alpha

2017 ◽  
Vol 232 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Maryam Iravani ◽  
Marie Lagerquist ◽  
Claes Ohlsson ◽  
Lars Sävendahl
Keyword(s):  
Estrogen Receptor ◽  
Side Effects ◽  
Growth Plate ◽  
Bone Growth ◽  
High Dose ◽  
Tall Stature ◽  
Plate Height ◽  
Estrogenic Effects ◽  
Increased Risk ◽  
Risk Of Cancer

Estrogens are well known for their capacity to promote bone maturation and at high doses to induce growth plate closure and thereby stop further growth. High-dose estrogen treatment has therefore been used to limit growth in extremely tall girls. However, recent data suggest that this treatment may have severe side effects, including increased risk of cancer and reduced fertility. We hypothesized that estrogenic effects in bone are mediated via ERα signaling. Twelve-week-old ovariectomized female C57BL/6 mice were subcutaneously injected for 4 weeks with E2 or selective ERα (PPT) or ERβ (DPN) agonists. After killing, tibia and femur lengths were measured, and growth plate morphology was analyzed. E2- and PPT-treated mice had shorter tibiae and femur bones when compared to vehicle-treated controls, whereas animals treated with DPN had similar bone lengths compared to controls. Growth plate height and hypertrophic zone height were reduced in animals treated with E2 or PPT but not in those treated with DPN, supporting that the effect was mediated via ERα. Moreover, PCNA staining revealed suppressed proliferation of chondrocytes in the tibia growth plate in PPT- or E2-treated mice compared to controls. Our data show that estrogenic effects on bone growth and growth plate maturation are mainly mediated via ERα. Our findings may have direct implications for the development of new and more selective treatment modalities of extreme tall stature using selective estrogen receptor modulators that may have low side effects than high-dose E2 treatment.

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.

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