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

Characterization of Voltage-Sensitive Calcium Channels in Growth Plate Chondrocytes

1997 ◽  
Vol 234 (2) ◽  
pp. 432-438 ◽  
Author(s):  
Michael J. Zuscik ◽  
Thomas E. Gunter ◽  
J.Edward Puzas ◽  
Randy N. Rosier
Keyword(s):  
Calcium Channels ◽  
Growth Plate ◽  
Growth Plate Chondrocytes

scholarly journals Loss of Foxc1 and Foxc2 function in chondroprogenitor cells disrupts endochondral ossification

2021 ◽  
Author(s):  
Asra Almubarak ◽  
Rotem Lavy ◽  
Nikola Srnic ◽  
Yawen Hu ◽  
Devi P. Maripuri ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Chondrocyte Differentiation ◽  
Growth Plate Chondrocytes ◽  
Chondroprogenitor Cells

AbstractEndochondral ossification forms and grows the majority of the mammalian skeleton and is tightly controlled through gene regulatory networks. The forkhead box transcription factors Foxc1 and Foxc2 have been demonstrated to regulate aspects of osteoblast function in the formation of the skeleton but their roles in chondrocytes to control endochondral ossification are less clear. We demonstrate that Foxc1 expression is directly regulated by SOX9 activity, one of the earliest transcription factors to specify the chondrocyte lineages. Moreover we demonstrate that elevelated expression of Foxc1 promotes chondrocyte differentiation in mouse embryonic stem cells and loss of Foxc1 function inhibits chondrogenesis in vitro. Using chondrocyte-targeted deletion of Foxc1 and Foxc2 in mice, we reveal a role for these factors in chondrocyte differentiation in vivo. Loss of both Foxc1 and Foxc2 caused a general skeletal dysplasia predominantly affecting the vertebral column. The long bones of the limb were smaller and mineralization was reduced and organization of the growth plate was disrupted. In particular, the stacked columnar organization of the proliferative chondrocyte layer was reduced in size and cell proliferation in growth plate chondrocytes was reduced. Differential gene expression analysis indicated disrupted expression patterns in chondrogenesis and ossification genes throughout the entire process of endochondral ossification in Col2-cre;Foxc1Δ/Δ;Foxc2Δ/Δ embryos. Our results suggest that Foxc1 and Foxc2 are required for correct chondrocyte differentiation and function. Loss of both genes results in disorganization of the growth plate, reduced chondrocyte proliferation and delays in chondrocyte hypertrophy that prevents correct ossification of the endochondral skeleton.

scholarly journals The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification

2011 ◽  
Vol 211 (2) ◽  
pp. 109-121 ◽  
Author(s):  
E J Mackie ◽  
L Tatarczuch ◽  
M Mirams
Keyword(s):  
Growth Factors ◽  
Growth Plate ◽  
Bone Morphogenetic Proteins ◽  
Endochondral Ossification ◽  
Bone Cells ◽  
Cartilage Tissue ◽  
Growth Plate Chondrocytes ◽  
Growth Plate Chondrocyte ◽  
Functional Complex ◽  
Endothelial Growth Factor

Endochondral ossification is the process that results in both the replacement of the embryonic cartilaginous skeleton during organogenesis and the growth of long bones until adult height is achieved. Chondrocytes play a central role in this process, contributing to longitudinal growth through a combination of proliferation, extracellular matrix (ECM) secretion and hypertrophy. Terminally differentiated hypertrophic chondrocytes then die, allowing the invasion of a mixture of cells that collectively replace the cartilage tissue with bone tissue. The behaviour of growth plate chondrocytes is tightly regulated at all stages of endochondral ossification by a complex network of interactions between circulating hormones (including GH and thyroid hormone), locally produced growth factors (including Indian hedgehog, WNTs, bone morphogenetic proteins and fibroblast growth factors) and the components of the ECM secreted by the chondrocytes (including collagens, proteoglycans, thrombospondins and matrilins). In turn, chondrocytes secrete factors that regulate the behaviour of the invading bone cells, including vascular endothelial growth factor and receptor activator of NFκB ligand. This review discusses how the growth plate chondrocyte contributes to endochondral ossification, with some emphasis on recent advances.

FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: Implications for endochondral ossification

2005 ◽  
Vol 24 (8) ◽  
pp. 520-529 ◽  
Author(s):  
S. Weizmann ◽  
A. Tong ◽  
A. Reich ◽  
O. Genina ◽  
A. Yayon ◽  
...  
Keyword(s):  
Growth Plate ◽  
Endochondral Ossification ◽  
Epiphyseal Growth Plate ◽  
Growth Plate Chondrocytes

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.

scholarly journals Thyroid Hormone Enhances Aggrecanase-2/ADAM-TS5 Expression and Proteoglycan Degradation in Growth Plate Cartilage

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2480-2488 ◽  
Author(s):  
Seicho Makihira ◽  
Weiqun Yan ◽  
Hiroshi Murakami ◽  
Masae Furukawa ◽  
Toshihisa Kawai ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Growth Plate ◽  
Cleavage Site ◽  
Endochondral Ossification ◽  
Core Protein ◽  
Binding Capacity ◽  
Mrna Level ◽  
Cartilage Explants ◽  
Type I ◽  
Proteoglycan Degradation

Abstract Effects of thyroid hormone on proteoglycan degradation in various regions of cartilage were investigated. In propylthiouracil-treated rats with hypothyroidism, proteoglycan degradation in epiphyseal cartilage during endochondral ossification was markedly suppressed. However, injections of T4 reversed this effect of propylthiouracil on proteoglycan degradation. In pig growth plate explants, T3 also induced breakdown of proteoglycan. T3 increased the release of aggrecan monomer and core protein from the explants into the medium. Accordingly, the level of aggrecan monomer remaining in the tissue decreased after T3 treatment, and the monomer lost hyaluronic acid-binding capacity, suggesting that the cleavage site is in the interglobular domain. The aggrecan fragment released from the T3-exposed explants underwent cleavage at Glu373-Ala374, the major aggrecanase-cleavage site. The stimulation of proteoglycan degradation by T3 was less prominent in resting cartilage explants than in growth plate explants and was barely detectable in articular cartilage explants. Using rabbit growth plate chondrocyte cultures, we explored proteases that may be involved in T3-induced aggrecan degradation and found that T3 enhanced the expression of aggrecanase-2/ADAM-TS5 (a disintegrin and a metalloproteinase domain with thrombospondin type I domains) mRNA, whereas we could not detect any enhancement of stromelysin, gelatinase, or collagenase activities or any aggrecanase-1/ADAM-TS4 mRNA expression. We also found that the aggrecanse-2 mRNA level, but not aggrecanase-1, increased at the hypertrophic stage during endochondral ossification. These findings suggest that aggrecanse-2/ADAM-TS5 is involved in aggrecan breakdown during endochondral ossification, and that thyroid hormone stimulates the aggrecan breakdown partly via the enhancement of aggrecanase-2/ADAM-TS5.

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
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