Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification.

Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Research Abstract Details 

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Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Abstract Text:

Makoto Hirao,Noriyuki Tamai,Noriyuki Tsumaki,Hideki Yoshikawa,Akira Myoui,

Cartilage functions at a lower oxygen tension than most other tissues. To determine the role of oxygen tension in chondrocyte differentiation and function, we investigated the influence of oxygen tension in the pluripotent mesenchymal cell line C3H10T1/2 and 14.5E mice embryo forelimb organ culture. 10T1/2 cells and embryo forelimbs were cultured under normoxia (20% O2) or hypoxia (5% O2) in the presence of recombinant human bone morphogenetic protein 2. To elucidate the mechanism by which oxygen tension influences chondrocyte differentiation, the Smad pathway was examined using Smad6 overexpression adenovirus and Smad6 transgenic mice embryo forelimbs. The p38 MAPK pathway was examined using dominant-negative MKK3 and FR167653, a specific p38 MAPK inhibitor. The transcriptional activities of Sox9 and Runx2 were also investigated. Hypoxia promoted bone morphogenetic protein 2-induced glycosaminoglycan production and suppressed alkaline phosphatase activity and mineralization of C3H10T1/2. Thus, hypoxia promoted chondrocytic commitment rather than osteoblastic differentiation. In the mice embryo forelimb organ culture, hypoxia increased cartilaginous matrix synthesis. These effects were primarily mediated by p38 MAPK activation, independent of Sox9. Hypoxia inhibited Col10a1 (type X collagen alpha1) expression via down-regulation of Runx2 activity by Smad suppression and histone deacetylase 4 activation. In conclusion, hypoxia promotes chondrocytic differentiation and cartilage matrix synthesis and suppresses terminal chondrocyte differentiation. These hypoxia-induced phenomena may act on chondrocytes to enhance and preserve their phenotype and function during chondrocyte differentiation and endochondral ossification.

Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Publishing Authors By Initials

M Hirao,N Tamai,N Tsumaki,H Yoshikawa,A Myoui,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research

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Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 31079-92

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 11

MONTH: 08

YEAR: 2006

Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Keywords Mesh Terms:

KEYWORDS: p38 Mitogen-Activated Protein Kinases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. Information

Substance Name: p38 Mitogen-Activated Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification.

AFFILIATION: Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadoaka, Suita, Osaka 565-0871, Japan.

Country: United States

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MEDLINETA: J Biol Chem

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