Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis
| Autor: | Hilda I. Aguirre-Sánchez, René Fernando Abarca-Buis, Juan B. Kouri, Clemente Ibarra, David Garciadiego-Cázares, Cristina Velasquillo |
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| Rok vydání: | 2014 |
| Předmět: |
Cartilage
Articular Male Cellular differentiation Bone Morphogenetic Protein 7 Integrin lcsh:Medicine Integrin alpha5 Chondrocyte Mice Chondrocytes Growth Differentiation Factor 5 Osteoarthritis medicine Animals Hedgehog Proteins Rats Wistar lcsh:Science Endochondral ossification Multidisciplinary biology Cartilage Integrin beta1 lcsh:R Growth differentiation factor Cell Differentiation Integrin alphaV Fibrosis Cell biology Extracellular Matrix Bone morphogenetic protein 7 medicine.anatomical_structure Immunology embryonic structures biology.protein lcsh:Q Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 5, p e0127166 (2015) |
| ISSN: | 1932-6203 |
| Popis: | The Integrin β1 family is the major receptors of the Extracellular matrix (ECM), and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA). In this scenario, integrins modify their pattern expression and regulate chondrocyte differen-tiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Su-perfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedif-ferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressedαV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of theα5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh), Gdf-5 and α5 integrin to maintain articular cartilage and prevent hy-pertrophy. |
| Databáze: | OpenAIRE |
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