title: Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis.
abstract: 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 differentiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Superfamily, 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 dedifferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressed αV 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 the α5 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 hypertrophy.
authors.affiliation: Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación (INR), Secretaría de Salud (SSA), Mexico City, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Garciadiego-Cázares
authors.affiliation: Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación (INR), Secretaría de Salud (SSA), Mexico City, Mexico.
authors.forename: Hilda I
authors.initials: HI
authors.lastname: Aguirre-Sánchez
authors.affiliation: Laboratorio de Tejido Conjuntivo, Instituto Nacional de Rehabilitación (INR), Secretaría de Salud (SSA), Mexico City, Mexico.
authors.forename: René F
authors.initials: RF
authors.lastname: Abarca-Buis
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico.
authors.forename: Juan B
authors.initials: JB
authors.lastname: Kouri
authors.affiliation: Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación (INR), Secretaría de Salud (SSA), Mexico City, Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Velasquillo
authors.affiliation: Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación (INR), Secretaría de Salud (SSA), Mexico City, Mexico.
authors.forename: Clemente
authors.initials: C
authors.lastname: Ibarra
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D055428:Growth Differentiation Factor 5 / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D055419:Bone Morphogenetic Protein 7; D055428:Growth Differentiation Factor 5; D053823:Hedgehog Proteins; D039482:Integrin alpha5; D039564:Integrin alphaV; D019012:Integrin beta1