Functions of transforming growth factor-beta family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes.

Détails

ID Serval
serval:BIB_12FB7A9F53DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Functions of transforming growth factor-beta family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes.
Périodique
Journal of Biological Chemistry
Auteur(s)
Valcourt U., Gouttenoire J., Moustakas A., Herbage D., Mallein-Gerin F.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2002
Volume
277
Numéro
37
Pages
33545-33558
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
We investigated the effects of bone morphogenetic protein (BMP)-2, a member of the transforming growth factor-beta superfamily, on the regulation of the chondrocyte phenotype, and we identified signaling molecules involved in this regulation. BMP-2 triggers three concomitant responses in mouse primary chondrocytes and chondrocytic MC615 cells. First, BMP-2 stimulates expression or synthesis of type II collagen. Second, BMP-2 induces expression of molecular markers characteristic of pre- and hypertrophic chondrocytes, such as Indian hedgehog, parathyroid hormone/parathyroid hormone-related peptide receptor, type X collagen, and alkaline phosphatase. Third, BMP-2 induces osteocalcin expression, a specific trait of osteoblasts. Constitutively active forms of transforming growth factor-beta family type I receptors and Smad proteins were overexpressed to address their role in this process. Activin receptor-like kinase (ALK)-1, ALK-2, ALK-3, and ALK-6 were able to reproduce the hypertrophic maturation of chondrocytes induced by BMP-2. In addition, ALK-2 mimicked further the osteoblastic differentiation of chondrocytes induced by BMP-2. In the presence of BMP-2, Smad1, Smad5, and Smad8 potentiated the hypertrophic maturation of chondrocytes, but failed to induce osteocalcin expression. Smad6 and Smad7 impaired chondrocytic expression and osteoblastic differentiation induced by BMP-2. Thus, our results indicate that Smad-mediated pathways are essential for the regulation of the different steps of chondrocyte and osteoblast differentiation and suggest that additional Smad-independent pathways might be activated by ALK-2.
Mots-clé
Activin Receptors, Type I/physiology, Animals, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins/pharmacology, Cell Differentiation, Cell Line, Chondrocytes/drug effects, Chondrocytes/physiology, Collagen Type II/genetics, DNA-Binding Proteins/physiology, Humans, Hypertrophy, Mice, Osteoblasts/drug effects, Osteoblasts/physiology, Protein-Serine-Threonine Kinases, Proteins, Receptors, Transforming Growth Factor beta/physiology, Smad Proteins, Smad1 Protein, Trans-Activators/physiology, Transforming Growth Factor beta
Pubmed
Open Access
Oui
Création de la notice
01/10/2015 16:20
Dernière modification de la notice
20/08/2019 13:41
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