scholarly journals mir-374-5p, mir-379-5p, and mir-503-5p Regulate Proliferation and Hypertrophic Differentiation of Growth Plate Chondrocytes in Male Rats

Endocrinology ◽  
2018 ◽  
Vol 159 (3) ◽  
pp. 1469-1478 ◽  
Author(s):  
Youn Hee Jee ◽  
Jinhee Wang ◽  
Shanna Yue ◽  
Melissa Jennings ◽  
Samuel J Clokie ◽  
...  
Keyword(s):  
Growth Plate ◽  
Male Rats ◽  
Growth Plate Chondrocytes

scholarly journals Gradients in bone morphogenetic protein-related gene expression across the growth plate

2007 ◽  
Vol 193 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Ola Nilsson ◽  
Elizabeth A Parker ◽  
Anita Hegde ◽  
Michael Chau ◽  
Kevin M Barnes ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Morphogenetic Proteins ◽  
Bmp Signaling ◽  
Male Rats ◽  
Quiescent State ◽  
Growth Plate Chondrocytes ◽  
Proliferative Zone ◽  
Morphogenetic Protein ◽  
Proliferation And Differentiation ◽  
Signaling Inhibitors

In the growth plate, stem-like cells in the resting zone differentiate into rapidly dividing chondrocytes of the proliferative zone and then terminally differentiate into the non-dividing chondrocytes of the hypertrophic zone. To explore the molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from the resting (RZ), proliferative (PZ), and hypertrophic zones (HZ) of 7-day-old male rats. Expression of approximately 29 000 genes was analyzed by microarray and selected genes verified by real-time PCR. The analysis identified genes whose expression changed dramatically during the differentiation program, including multiple genes functionally related to bone morphogenetic proteins (BMPs). BMP-2 and BMP-6 were upregulated in HZ compared with RZ and PZ (30-fold each, P < 0.01 and 0.001 respectively). In contrast, BMP signaling inhibitors were expressed early in the differentiation pathway; BMP-3 and gremlin were differentially expressed in RZ (100- and 80-fold, compared with PZ, P < 0.001 and 0.005 respectively) and growth differentiation factor (GDF)-10 in PZ (160-fold compared with HZ, P < 0.001). Our findings suggest a BMP signaling gradient across the growth plate, which is established by differential expression of multiple BMPs and BMP inhibitors in specific zones. Since BMPs can stimulate both proliferation and hypertrophic differentiation of growth plate chondrocytes, these findings suggest that low levels of BMP signaling in the resting zone may help maintain these cells in a quiescent state. In the lower RZ, greater BMP signaling may help induce differentiation to proliferative chondrocytes. Farther down the growth plate, even greater BMP signaling may help induce hypertrophic differentiation. Thus, BMP signaling gradients may be a key mechanism responsible for spatial regulation of chondrocyte proliferation and differentiation in growth plate cartilage.

scholarly journals Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes

2003 ◽  
Vol 176 (3) ◽  
pp. 331-337 ◽  
Author(s):  
D Chrysis ◽  
EM Ritzen ◽  
L Savendahl
Keyword(s):  
Growth Plate ◽  
Growth Retardation ◽  
Caspase 3 ◽  
Male Rats ◽  
Apoptotic Cells ◽  
Growth Plate Chondrocytes ◽  
Glucocorticoid Treatment ◽  
Local Mechanism ◽  
Apoptotic Proteins ◽  
Multicellular Organisms

Glucocorticoids cause significant growth retardation in mammals and humans and decreased proliferation of chondrocytes has been considered as the main local mechanism. Death by apoptosis is an important regulator of homeostasis in multicellular organisms. Here we chose to study the role of apoptosis in growth retardation caused by glucocorticoid treatment. We treated 7-week-old male rats with dexamethasone (5 mg/kg/day) for 7 days. Apoptosis was studied in tibiae growth plates by the TUNEL method. Immunoreactivity for parathyroid hormone-related peptide (PTHrP), caspase-3, and the anti-apoptotic proteins Bcl-2 and Bcl-x was also studied. Apoptosis was mainly localized in terminal hypertropic chondrocytes (THCs) in both control and dexamethasone-treated animals. Dexamethasone caused an increase in apoptosis which was fourfold in THCs (2.45+/-0.12 vs 0.62+/-0.09 apoptotic cells/mm growth plate, P<0.001), and 18-fold in proliferative chondrocytes (0.18+/-0.04 vs 0.01+/-0.007 apoptotic cells/mm growth plate, P<0.001). Increased apoptosis after dexamethasone treatment was accompanied by increased immunoreactivity for caspase-3 and decreased immunoreactivity for the anti-apoptotic proteins Bcl-2 and Bcl-x, which further supports our apoptosis results. Dexamethasone also decreased the immunoreactivity for PTHrP, suggesting a role in the mechanism by which glucocorticoids induce apoptosis in the growth plate. We conclude that apoptosis is one mechanism involved in growth retardation induced by glucocorticoids. Premature loss of resting/proliferative chondrocytes by apoptosis could contribute to incomplete catch-up seen after prolonged glucocorticoid treatment.

scholarly journals Expression and Functional Assessment of an Alternatively Spliced Extracellular Ca2+-Sensing Receptor in Growth Plate Chondrocytes

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5294-5303 ◽  
Author(s):  
Luis Rodriguez ◽  
Chialing Tu ◽  
Zhiqiang Cheng ◽  
Tsui-Hua Chen ◽  
Daniel Bikle ◽  
...  
Keyword(s):  
Cell Surface ◽  
Growth Plate ◽  
Inositol Phosphate ◽  
Intact Cell ◽  
Chinese Hamster ◽  
Full Length ◽  
Wild Type ◽  
Growth Plate Chondrocytes ◽  
Matrix Gene ◽  
Alternatively Spliced

The extracellular Ca2+-sensing receptor (CaR) plays an essential role in mineral homeostasis. Studies to generate CaR-knockout (CaR−/−) mice indicate that insertion of a neomycin cassette into exon 5 of the mouse CaR gene blocks the expression of full-length CaRs. This strategy, however, allows for the expression of alternatively spliced CaRs missing exon 5 [Exon5(−)CaRs]. These experiments addressed whether growth plate chondrocytes (GPCs) from CaR−/− mice express Exon5(−)CaRs and whether these receptors activate signaling. RT-PCR and immunocytochemistry confirmed the expression of Exon5(−)CaR in growth plates from CaR−/− mice. In Chinese hamster ovary or human embryonic kidney-293 cells, recombinant human Exon5(−)CaRs failed to activate phospholipase C likely due to their inability to reach the cell surface as assessed by intact-cell ELISA and immunocytochemistry. Human Exon5(−)CaRs, however, trafficked normally to the cell surface when overexpressed in wild-type or CaR−/− GPCs. Immunocytochemistry of growth plate sections and cultured GPCs from CaR−/− mice showed easily detectable cell-membrane expression of endogenous CaRs (presumably Exon5(−)CaRs), suggesting that trafficking of this receptor form to the membrane can occur in GPCs. In GPCs from CaR−/− mice, high extracellular [Ca2+] ([Ca2+]e) increased inositol phosphate production with a potency comparable with that of wild-type GPCs. Raising [Ca2+]e also promoted the differentiation of CaR−/− GPCs as indicated by changes in proteoglycan accumulation, mineral deposition, and matrix gene expression. Taken together, our data support the idea that expression of Exon5(−)CaRs may compensate for the loss of full-length CaRs and be responsible for sensing changes in [Ca2+]e in GPCs in CaR−/− mice.

L-type calcium channels in growth plate chondrocytes participate in endochondral ossification

2007 ◽  
Vol 101 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Edna E. Mancilla ◽  
Mario Galindo ◽  
Barbara Fertilio ◽  
Mario Herrera ◽  
Karime Salas ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Growth Plate Chondrocytes

scholarly journals Differential effects of insulin-like growth factor binding proteins-1, -2, -3, and -6 on cultured growth plate chondrocytes

2002 ◽  
Vol 62 (5) ◽  
pp. 1591-1600 ◽  
Author(s):  
Daniela Kiepe ◽  
Tim Ulinski ◽  
David R. Powell ◽  
Susan K. Durham ◽  
Otto Mehls ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Plate ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Growth Plate Chondrocytes ◽  
Differential Effects ◽  
Factor Binding

Investigation of RARg Signaling in Human Growth-Plate Chondrocytes

2021 ◽  
Author(s):  
Joshua M. Abzug ◽  
Hongying Tian ◽  
Masatake Matsuoka ◽  
Danielle A. Hogarth ◽  
Casey M. Codd ◽  
...  
Keyword(s):  
Growth Plate ◽  
Human Growth ◽  
Growth Plate Chondrocytes

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 Selective enrichment of microRNAs in extracellular matrix vesicles produced by growth plate chondrocytes

Bone ◽  
2016 ◽  
Vol 88 ◽  
pp. 47-55 ◽  
Author(s):  
Zhao Lin ◽  
Nicholas E. Rodriguez ◽  
Junjun Zhao ◽  
Allison N. Ramey ◽  
Sharon L. Hyzy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Plate ◽  
Matrix Vesicles ◽  
Growth Plate Chondrocytes ◽  
Selective Enrichment
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