Osterix Regulates Calcification and Degradation of Chondrogenic Matrices through Matrix Metalloproteinase 13 (MMP13) Expression in Association with Transcription Factor Runx2 during Endochondral Ossification
| Autor: | Toshiyuki Yoneda, Shiho Honma, Haruhiko Akiyama, Makoto Wakabayashi, Go Shioi, Satoshi Wakisaka, Takuma Matsubara, Akira Yamaguchi, Kenji Hata, Riko Nishimura, Hiroshi Kiyonari, Noriyuki Tsumaki |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Core Binding Factor Alpha 1 Subunit Mice Transgenic Cartilage metabolism SOX9 Transfection Biochemistry Chondrocyte Mice Internal medicine Matrix Metalloproteinase 13 Osteoarthritis medicine Animals Humans Sp7 Transcription Factor Molecular Biology Endochondral ossification Oligonucleotide Array Sequence Analysis Mice Knockout Chemistry Ossification musculoskeletal neural and ocular physiology Cell Differentiation Cell Biology Chondrogenesis Up-Regulation Cell biology RUNX2 Cartilage medicine.anatomical_structure Endocrinology medicine.symptom Developmental Biology Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 287:33179-33190 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.337063 |
| Popis: | Endochondral ossification is temporally and spatially regulated by several critical transcription factors, including Sox9, Runx2, and Runx3. Although the molecular mechanisms that control the late stages of endochondral ossification (e.g. calcification) are physiologically and pathologically important, these precise regulatory mechanisms remain unclear. Here, we demonstrate that Osterix is an essential transcription factor for endochondral ossification that functions downstream of Runx2. The global and conditional Osterix-deficient mice studied here exhibited a defect of cartilage-matrix ossification and matrix vesicle formation. Importantly, Osterix deficiencies caused the arrest of endochondral ossification at the hypertrophic stage. Microarray analysis revealed that matrix metallopeptidase 13 (MMP13) is an important target of Osterix. We also showed that there exists a physical interaction between Osterix and Runx2 and that these proteins function cooperatively to induce MMP13 during chondrocyte differentiation. Most interestingly, the introduction of MMP13 stimulated the calcification of matrices in Osterix-deficient mouse limb bud cells. Our results demonstrated that Osterix was essential to endochondral ossification and revealed that the physical and functional interaction between Osterix and Runx2 were necessary for the induction of MMP13 during endochondral ossification. |
| Databáze: | OpenAIRE |
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