Reference - Detail
| RRC ID | 43417 |
|---|---|
| Author | Oshima Y, Akiyama T, Hikita A, Iwasawa M, Nagase Y, Nakamura M, Wakeyama H, Kawamura N, Ikeda T, Chung UI, Hennighausen L, Kawaguchi H, Nakamura K, Tanaka S. |
| Title | Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis. |
| Journal | J Biol Chem |
| Abstract |
During endochondral ossification, chondrocytes undergo hypertrophic differentiation and die by apoptosis. The level of inorganic phosphate (P(i)) elevates at the site of cartilage mineralization, and when chondrocytes were treated with P(i), they underwent rapid apoptosis. Gene silencing of the proapoptotic Bcl-2 homology 3-only molecule bnip3 significantly suppressed P(i)-induced apoptosis. Conversely, overexpression of Bcl-xL suppressed, and its knockdown promoted, the apoptosis of chondrocytes. Bnip3 was associated with Bcl-xL in chondrocytes stimulated with P(i). Bcl-xL was expressed uniformly in the growth plate chondrocytes, whereas Bnip3 expression was exclusively localized in the hypertrophic chondrocytes. Finally, we generated chondrocyte-specific bcl-x knock-out mice using the Cre-loxP recombination system, and we provided evidence that the hypertrophic chondrocyte layer was shortened in those mice because of an increased apoptosis of prehypertrophic and hypertrophic chondrocytes, with the mice afflicted with dwarfism as a result. These results suggest the pivotal role of Bcl-2 family members in the regulation of chondrocyte apoptosis. |
| Volume | 283(39) |
| Pages | 26499-508 |
| Published | 2008-9-26 |
| DOI | 10.1074/jbc.M800933200 |
| PII | S0021-9258(20)52394-6 |
| PMID | 18632667 |
| PMC | PMC2546555 |
| MeSH | Animals Apoptosis / drug effects Apoptosis / physiology* Calcification, Physiologic / drug effects Calcification, Physiologic / physiology Cartilage / cytology Cartilage / metabolism Chondrocytes / cytology Chondrocytes / metabolism* Dwarfism / genetics Dwarfism / metabolism Gene Silencing Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Knockout Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Phosphates / metabolism Phosphates / pharmacology Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2 bcl-X Protein / genetics bcl-X Protein / metabolism* |
| IF | 4.238 |
| Times Cited | 28 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |