scholarly journals PTHrP targets salt-inducible kinases, HDAC4 and HDAC5, to repress chondrocyte hypertrophy in the growth plate

Bone ◽  
2021 ◽  
Vol 142 ◽  
pp. 115709
Author(s):  
Shigeki Nishimori ◽  
Marc N. Wein ◽  
Henry M. Kronenberg
Keyword(s):  
Growth Plate ◽  
Chondrocyte Hypertrophy

Microbiota‐derived lipopolysaccharide retards chondrocyte hypertrophy in the growth plate through elevating Sox9 expression

2018 ◽  
Vol 234 (3) ◽  
pp. 2593-2605 ◽  
Author(s):  
Xin Cheng ◽  
Pei‐Zhi Li ◽  
Guang Wang ◽  
Yu Yan ◽  
Ke Li ◽  
...  
Keyword(s):  
Growth Plate ◽  
Sox9 Expression ◽  
Chondrocyte Hypertrophy

Critical roles for chemokine SDF-1 signaling in the development of growth plate chondrocyte hypertrophy

Bone ◽  
2008 ◽  
Vol 43 ◽  
pp. S32
Author(s):  
Lei Wei ◽  
Xiaojuan Sun ◽  
Katsuaki Kanbe ◽  
Richard Terek ◽  
Qian Chen
Keyword(s):  
Growth Plate ◽  
Chondrocyte Hypertrophy ◽  
Growth Plate Chondrocyte

scholarly journals Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures

Endocrinology ◽  
2004 ◽  
Vol 145 (5) ◽  
pp. 2478-2486 ◽  
Author(s):  
T. Mushtaq ◽  
P. Bijman ◽  
S. F. Ahmed ◽  
C. Farquharson
Keyword(s):  
Growth Plate ◽  
Growth Retardation ◽  
Bone Growth ◽  
Cellular Level ◽  
Similar Degree ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Growth Inhibitory ◽  
Fetal Mice ◽  
Igf I

Abstract The study aims were to improve our understanding of the mechanisms of glucocorticoid-induced growth retardation at the growth plate and determine whether IGF-I could ameliorate the effects. Fetal mouse metatarsals were cultured for up to 10 d with dexamethasone (Dex; 10–6m) and/or IGF-I and GH (both at 100 ng/ml). Both continuous and alternate-day Dex treatment inhibited bone growth to a similar degree, whereas IGF-I alone or together with Dex caused an increase in bone growth. GH had no effects. These observations may be explained at the cellular level; cell proliferation within the growing bone was decreased by Dex and increased by IGF-I and these effects were more marked in the cells of the perichondrium than those in the growth plate. However, the most prominent observation was noted in the hypertrophic zone where all treatments containing IGF-I significantly increased (3-fold) the length of this zone, whereas Dex alone had no significant effect. In conclusion, Dex impaired longitudinal growth by inhibiting chondrocyte proliferation, whereas IGF-I stimulated chondrocyte hypertrophy and reversed the growth-inhibitory Dex effects. However, the IGF-I-mediated improvement in growth was at the expense of altering the balance between proliferating and hypertrophic chondrocytes within the metatarsal.

scholarly journals Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth

2004 ◽  
Vol 180 (2) ◽  
pp. 247-255 ◽  
Author(s):  
J Wang ◽  
J Zhou ◽  
CM Cheng ◽  
JJ Kopchick ◽  
CA Bondy
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
Long Bone ◽  
Null Mouse ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Longitudinal Bone Growth ◽  
Germinal Zone ◽  
Igf I

The possibility that growth hormone (GH) has effects on long bone growth independent of insulin-like growth factor-I (IGF-I) has long been debated. If this is true, then long bone growth should be more profoundly affected by the absence of GH (since both GH and GH-stimulated IGF-I effects are absent) than by the absence of IGF-I alone (since GH is still present and actually elevated). To test this hypothesis, we compared long bone growth in mice with targeted deletions of Igf1 vs growth hormone receptor (Ghr). Tibial linear growth rate was reduced by approximately 35% in Igf1 null mice and by about 65% in Ghr null mice between postnatal days 20 and 40, a time of peak GH effect during normal longitudinal growth. The Igf1 null mouse growth plate demonstrated significant enlargement of the germinal zone; chondrocyte proliferation and numbers were normal but chondrocyte hypertrophy was significantly reduced. In contrast, the Ghr null mouse germinal zone was hypoplastic, chondrocyte proliferation and numbers were significantly reduced, and chondrocyte hypertrophy was also reduced. We have previously demonstrated that IGF-II is highly expressed in growth plate germinal and proliferative zones, so we considered the possibility that GH-stimulated IGF-II production might promote germinal zone expansion and maintain normal proliferation in the Igf1 null mouse growth plate. Supporting this view, IGF-II mRNA was increased in the Igf1 null mouse and decreased in the Ghr null mouse growth plate.Thus, in the complete absence of IGF-I but in the presence of elevated GH in the Igf1 null mouse, reduction in chondrocyte hypertrophy appears to be the major defect in longitudinal bone growth. In the complete absence of a GH effect in the Ghr null mouse, however, both chondrocyte generation and hypertrophy are compromised, leading to a compound deficit in long bone growth. These observations support dual roles for GH in promoting longitudinal bone growth: an IGF-I-independent role in growth plate chondrocyte generation and an IGF-I-dependent role in promoting chondrocyte hypertrophy. The question of whether GH has direct effects on chondrocyte generation is still not settled, however, since it now appears that IGF-II may medicate some of these effects on the growth plate.

Wnt/β-catenin Signaling Regulates Cranial Base Development and Growth

2008 ◽  
Vol 87 (3) ◽  
pp. 244-249 ◽  
Author(s):  
M. Nagayama ◽  
M. Iwamoto ◽  
A. Hargett ◽  
N. Kamiya ◽  
Y. Tamamura ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Wnt Signaling ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Cranial Base ◽  
Developmental Changes ◽  
Chondrocyte Hypertrophy ◽  
Chondrocyte Maturation ◽  
Wnt Proteins ◽  
Deficient Mice

Wnt proteins and β-catenin signaling regulate major processes during embryonic development, and we hypothesized that they regulate cranial base synchondrosis development and growth. To address this issue, we analyzed cartilage-specific β -catenin-deficient mice. Mutant synchondroses lacked typical growth plate zones, and endochondral ossification was delayed. In reciprocal transgenic experiments, cartilage overexpression of a constitutive active Lef1, a transcriptional mediator of Wnt/β-catenin signaling, caused precocious chondrocyte hypertrophy and intermingling of immature and mature chondrocytes. The developmental changes seen in β -catenin-deficient synchondroses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signaling antagonist and a potential Ihh signaling target. Thus, Wnt/β-catenin signaling is essential for cranial base development and synchondrosis growth plate function. This pathway promotes chondrocyte maturation and ossification events, and may exert this important role by dampening the effects of Ihh-PTHrP together with sFRP-1.

scholarly journals Innovative Three-Dimensional Microscopic Analysis of Uremic Growth Plate Discloses Alterations in the Process of Chondrocyte Hypertrophy: Effects of Growth Hormone Treatment

2020 ◽  
Vol 21 (12) ◽  
pp. 4519
Author(s):  
Ángela Fernández-Iglesias ◽  
Rocío Fuente ◽  
Helena Gil-Peña ◽  
Laura Alonso-Durán ◽  
María García-Bengoa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Growth Hormone Treatment ◽  
Three Dimensional ◽  
Microscopic Analysis ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Chondrocyte Hypertrophy ◽  
Chondrocyte Maturation ◽  
And Function

Chronic kidney disease (CKD) alters the morphology and function of the growth plate (GP) of long bones by disturbing chondrocyte maturation. GP chondrocytes were analyzed in growth-retarded young rats with CKD induced by adenine intake (AD), control rats fed ad libitum (C) or pair-fed with the AD group (PF), and CKD rats treated with growth hormone (ADGH). In order to study the alterations in the process of GP maturation, we applied a procedure recently described by our group to obtain high-quality three-dimensional images of whole chondrocytes that can be used to analyze quantitative parameters like cytoplasm density, cell volume, and shape. The final chondrocyte volume was found to be decreased in AD rats, but GH treatment was able to normalize it. The pattern of variation in the cell cytoplasm density suggests that uremia could be causing a delay to the beginning of the chondrocyte hypertrophy process. Growth hormone treatment appears to be able to compensate for this disturbance by triggering an early chondrocyte enlargement that may be mediated by Nkcc1 action, an important membrane cotransporter in the GP chondrocyte enlargement.

Cellular scale model of growth plate: An in silico model of chondrocyte hypertrophy

2017 ◽  
Vol 428 ◽  
pp. 87-97 ◽  
Author(s):  
H.A. Castro-Abril ◽  
J.M. Guevara ◽  
M.A. Moncayo ◽  
S.J. Shefelbine ◽  
L.A. Barrera ◽  
...  
Keyword(s):  
Growth Plate ◽  
In Silico ◽  
Scale Model ◽  
Chondrocyte Hypertrophy ◽  
In Silico Model

Effects of Hypophysectomy on the Occurrence and Calcifiability of Matrix Vesicles in the Epiphyseal Growth Plate of Immature Rats

1980 ◽  
Vol 38 ◽  
pp. 578-579
Author(s):  
S. I. Coleman ◽  
W. J. Dougherty
Keyword(s):  
Growth Plate ◽  
Matrix Vesicles ◽  
Epiphyseal Growth Plate ◽  
Hard Tissue ◽  
Hormonal Factors ◽  
Post Surgery ◽  
Mineral Deposition ◽  
Thin Sectioning ◽  
Integral Role ◽  
Cellular Secretion

In the cellular secretion theory of mineral deposition, extracellular matrix vesicles are believed to play an integral role in hard tissue mineralization (1). Membrane limited matrix vesicles arise from the plasma membrane of epiphyseal chondrocytes and tooth odontoblasts by a budding process (2, 3). Nutritional and hormonal factors have been postulated to play essential roles in mineral deposition and apparently have a direct effect on matrix vesicles of calcifying cartilage as concluded by Anderson and Sajdera (4). Immature (75-85 gm) Long-Evans hooded rats were hypophysectomized by the parapharyngeal approach and maintained fourteen (14) days post-surgery. At this time, the animals were anesthetized and perfusion fixed in cacodylate buffered 2.5% glutaraldehyde. The proximal tibias were quickly dissected out and split sagittally. One half was used for light microscopy (LM) and the other for electron microscopy (EM). The halves used for EM were cut into blocks approximately 1×3 mm. The tissue blocks were prepared for ultra-thin sectioning and transmission EM. The tissue was oriented so as to section through the epiphyseal growth plate from the zone of proliferating cartilage on down through the hypertrophic zone and into the initial trabecular bone. Sections were studied stained (double heavy metal) and unstained.

MICROCHEMICAL ANALYSIS OF HUMAN TIBIAL GROWTH CARTILAGE IN VARIOUS FORMS OF DWARFISM

1972 ◽  
Vol 69 (4) ◽  
pp. 659-688 ◽  
Author(s):  
V. Stanescu ◽  
R. Stanescu ◽  
J. A. Szirmai
Keyword(s):  
Growth Plate ◽  
Chondroitin Sulphate ◽  
Epiphyseal Plate ◽  
Molecular Characteristics ◽  
Growth Disorders ◽  
Normal Children ◽  
Collagen Concentration ◽  
Vitamin D Resistant Rickets ◽  
Pooled Samples ◽  
Tibial Epiphyseal

ABSTRACT Microchemical determinations of glycosaminoglycans and collagen were preformed in isolated histological zones from sections of tibial epiphyseal plate biopsies obtained from children with growth disorders (pituitary dwarfism, congenital myxoedema, Turner's syndrome, Noonan's syndrome, mucopolysaccharidosis type VI, vitamin D resistant rickets and achondroplasia). Alternate sections were used for histochemical localization of glycosaminoglycans and proteins. The values were compared with those found in comparable zones of the growth plate from normal children of the same age. The chondroitin sulphate concentration (% of defatted dry wt.) in the normal epiphyseal plate increased from the resting zone towards the proliferating/hypertrophic zone; collagen exhibited a reverse trend. In some of the pathological biopsies the concentration of chondroitin sulphate was slightly decreased whereas that of collagen was slightly increased. A marked increase in the collagen concentration was found in achondroplasia. The solubility profiles of the cetylpyridinium complexes of the chondroitin sulphate fraction showed three main peaks with slight but characteristic differences in the various zones of the normal cartilage plate. Significant shifts in the proportion of these peaks were observed in several pathological biopsies, indicating possible deviations from the normal molecular characteristics of the chondroitin sulphate. Analysis of the main chondroitin sulphate fraction, obtained from pooled samples of normal tibial growth plate after fractionation on the macroscale, indicated that all three peaks contained both chondroitin-4 sulphate and chondroitin-6 sulphate and that they probably differed in their molecular weight.

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