Targeted Expression of SHH Affects Chondrocyte Differentiation, Growth Plate Organization, and Sox9 Expression

2004 ◽  
Vol 19 (10) ◽  
pp. 1678-1688 ◽  
Author(s):  
Sara Tavella ◽  
Roberta Biticchi ◽  
Anna Schito ◽  
Eleonora Minina ◽  
Davide Di Martino ◽  
...  
2018 ◽  
Vol 234 (3) ◽  
pp. 2593-2605 ◽  
Author(s):  
Xin Cheng ◽  
Pei‐Zhi Li ◽  
Guang Wang ◽  
Yu Yan ◽  
Ke Li ◽  
...  

1999 ◽  
Vol 144 (1) ◽  
pp. 161-173 ◽  
Author(s):  
Noriyuki Tsumaki ◽  
Kazuhiro Tanaka ◽  
Eri Arikawa-Hirasawa ◽  
Takanobu Nakase ◽  
Tomoatsu Kimura ◽  
...  

Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements.


2001 ◽  
Vol 169 (3) ◽  
pp. 573-579 ◽  
Author(s):  
I Sekiya ◽  
P Koopman ◽  
K Tsuji ◽  
S Mertin ◽  
V Harley ◽  
...  

SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are also known to promote chondrocyte differentiation via unknown molecular mechanisms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared from rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in these chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 24 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Western blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox- consensus sequence is located. The enhancing effect of DEX was specific to SOX9, as DEX did not alter the levels of Sox6 mRNA expression. These data suggest that DEX promotes chondrocyte differentiation through enhancement of SOX9.


2014 ◽  
Vol 53 (2) ◽  
pp. R39-R45 ◽  
Author(s):  
Andrei S Chagin ◽  
Henry M Kronenberg

Herein, we review the regulation of differentiation of the growth plate chondrocytes by G-proteins. In connection with this, we summarize the current knowledge regarding each family of G-protein α subunit, specifically, Gαs, Gαq/11, Gα12/13, and Gαi/o. We discuss different mechanisms involved in chondrocyte differentiation downstream of G-proteins and different G-protein-coupled receptors (GPCRs) activating G-proteins in the epiphyseal chondrocytes. We conclude that among all G-proteins and GPCRs expressed by chondrocytes, Gαshas the most important role and prevents premature chondrocyte differentiation. Receptor for parathyroid hormone (PTHR1) appears to be the major activator of Gαsin chondrocytes and ablation of either one leads to accelerated chondrocyte differentiation, premature fusion of the postnatal growth plate, and ultimately short stature.


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