title: Slug transcription factor and nuclear Lamin B1 are upregulated in osteoarthritic chondrocytes.
abstract: OBJECTIVE
  To contribute to clarify molecular mechanisms supporting senescence and de-differentiation of chondrocytes in chondrocyte pathologies such as osteoarthritis (OA). Specifically, we investigated the relationship between the nuclear lamina protein Lamin B1 and the negative regulator of chondrogenesis Slug transcription factor in osteoarthritic chondrocytes.
  
  
  METHODS
  Lamin B1 and Slug proteins were analyzed in cartilage explants from normal subjects and OA patients by immunohistochemical technique. Their expression was confirmed on isolated chondrocytes both at passage 0 and passage 2 (de-differentiated chondrocytes) by immunofluorescence and western blot. Subsequently, we explored the "in vivo" binding of Slug on LMNB1 promoter by chromatin immunoprecipitation assay (ChIP).
  
  
  RESULTS
  In this study we demonstrated that nuclear lamina protein Lamin B1 and anti-chondrogenic Slug transcription factor are upregulated in cartilage and OA chondrocytes. Furthermore, we found that Slug is "in vivo" recruited by LMNB1 gene promoter mostly when chondrocytes undergo de-differentiation or OA degeneration.
  
  
  CONCLUSIONS
  We described for the first time a potential regulatory role of Slug on the LMNB1 gene expression in OA chondrocytes. These findings may have important implications for the study of premature senescence, and degeneration of cartilage, and may contribute to develop effective therapeutic strategies against signals supporting cartilage damage in different subsets of patients.
authors: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy. Electronic address: piv@unife.it.
authors: R
authors: R
authors: Piva
authors: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors: E
authors: E
authors: Lambertini
authors: Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, IOR, Bologna, Italy; Laboratorio RAMSES, IOR, Bologna, Italy.
authors: C
authors: C
authors: Manferdini
authors: Rizzoli Orthopedic Institute, Laboratory of Musculoskeletal Cell Biology, and CNR Institute for Molecular Genetics, Bologna, Italy.
authors: C
authors: C
authors: Capanni
authors: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors: L
authors: L
authors: Penolazzi
authors: Laboratorio RAMSES, IOR, Bologna, Italy.
authors: E
authors: E
authors: Gabusi
authors: Laboratorio RAMSES, IOR, Bologna, Italy.
authors: F
authors: F
authors: Paolella
authors: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors: A
authors: A
authors: Lolli
authors: Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors: M
authors: M
authors: Angelozzi
authors: Rizzoli Orthopedic Institute, Laboratory of Musculoskeletal Cell Biology, and CNR Institute for Molecular Genetics, Bologna, Italy.
authors: G
authors: G
authors: Lattanzi
authors: Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, IOR, Bologna, Italy; Laboratorio RAMSES, IOR, Bologna, Italy.
authors: G
authors: G
authors: Lisignoli
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism; D007797:Laminin / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: C478221:LAMB1 protein, human; D007797:Laminin; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: Lamin B1; Osteoarthritis; Senescence; Slug