scholarly journals Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP

2005 ◽  
Vol 115 (7) ◽  
pp. 1734-1742 ◽  
Author(s):  
T. Kobayashi
2002 ◽  
Vol 277 (51) ◽  
pp. 50112-50120 ◽  
Author(s):  
Ming Shen ◽  
Eri Yoshida ◽  
Weiqun Yan ◽  
Takeshi Kawamoto ◽  
Ketut Suardita ◽  
...  

The mRNA level of basic helix-loop-helix transcription factor DEC1 (BHLHB2)/Stra13/Sharp2 was up-regulated during chondrocyte differentiation in cultures of ATDC5 cells and growth plate chondrocytes, and in growth plate cartilagein vivo. Forced expression of DEC1 in ATDC5 cells induced chondrogenic differentiation, and insulin increased this effect of DEC1 overexpression. Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) suppressed DEC1 expression and the differentiation of ATDC5 cells, but DEC1 overexpression antagonized this inhibitory action of PTH/PTHrP. Transforming growth factor-β or bone morphogenetic protein-2, as well as insulin, induced DEC1 expression in ATDC5 cultures where it induced chondrogenic differentiation. In pellet cultures of bone marrow mesenchymal stem cells exposed to transforming growth factor-β and insulin, DEC1 was induced at the earliest stage of chondrocyte differentiation and also at the hypertrophic stage. Overexpression of DEC1 in the mesenchymal cells induced the mRNA expressions of type II collagen, Indian hedgehog, and Runx2, as well as cartilage matrix accumulation; overexpression of DEC1 in growth plate chondrocytes at the prehypertrophic stage increased the mRNA levels of Indian hedgehog, Runx2, and type X collagen, and also increased alkaline phosphatase activity and mineralization. To our knowledge, DEC1 is the first transcription factor that can promote both chondrogenic differentiation and terminal differentiation.


Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2977-2986 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Ung-il Chung ◽  
Ernestina Schipani ◽  
Michael Starbuck ◽  
Gerard Karsenty ◽  
...  

In developing murine growth plates, chondrocytes near the articular surface (periarticular chondrocytes) proliferate, differentiate into flat column-forming proliferating cells (columnar chondrocytes), stop dividing and finally differentiate into hypertrophic cells. Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-related peptide (PTHrP) which negatively regulates terminal chondrocyte differentiation through the PTH/PTHrP receptor (PPR). However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte differentiation are unclear. We present novel mouse models with PPR abnormalities that help clarify these roles. In mice with chondrocyte-specific PPR ablation and mice with reduced PPR expression, chondrocyte differentiation was accelerated not only at the terminal step but also at an earlier step: periarticular to columnar differentiation. In these models, upregulation of Ihh action in the periarticular region was also observed. In the third model in which the PPR was disrupted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregulated because of ectopically differentiated hypertrophic chondrocytes that had lost PPR. Acceleration of periarticular to columnar differentiation was also noted in this mouse, while most of periarticular chondrocytes retained PPR signaling. These data suggest that Ihh positively controls differentiation of periarticular chondrocytes independently of PTHrP. Thus, chondrocyte differentiation is controlled at multiple steps by PTHrP and Ihh through the mutual regulation of their activities.


2013 ◽  
Vol 381 (1-2) ◽  
pp. 191-199 ◽  
Author(s):  
Kannikar Wongdee ◽  
Natchayaporn Thonapan ◽  
Wasana Saengamnart ◽  
Nateetip Krishnamra ◽  
Narattaphol Charoenphandhu

2010 ◽  
Vol 29 (6) ◽  
pp. 453-460 ◽  
Author(s):  
Benedetta Gualeni ◽  
Marcella Facchini ◽  
Fabio De Leonardis ◽  
Ruggero Tenni ◽  
Giuseppe Cetta ◽  
...  

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