Regulation of synovial cell function by adenovirus vector-mediated gene transduction

  • S Tanaka1,

    Affiliated with

    • H Seto1,

      Affiliated with

      • H Oda1 and

        Affiliated with

        • K Nakamura1

          Affiliated with

          Arthritis Res Ther20035(Suppl 3):18

          DOI: 10.1186/ar819

          Published: 12 September 2003

          It has been recently demonstrated that synovial fibroblasts (SFs) contain a multipotent mesenchymal cell population. To examine the chondrogenic potentialities of SFs in vitro and in vivo, SFs were isolated from knee joints of rabbits or rheumatoid arthritis patients, and infected with adenovirus vectors carrying LacZ (control), constitutively active forms of activin receptor like kinase (ALK)-3 or ALK-5 genes. Efficient gene transduction was confirmed by β-galactosidase staining of the LacZ virus-infected SFs. Northern blotting of type II collagen and aggrecan genes showed clear induction of these genes in SFs infected with ALK-3 virus, while no chondrogenic phenotypes were observed in LacZ or ALK-5-infected cells. ALK-3 virus-infected SFs were also positively stained by Alcian blue staining and type II collagen immunostaining. When transplanted into cartilage defects of rabbit knee joints, ALK-3 virus-infected rabbit SFs produced repair cartilage of hyaline morphology containing a type II collagen-positive matrix that restored the articular surface. These results suggest that adenovirus vector-mediated ALK-3 gene expression can induce chondrogenic differentiation of synovial fibroblasts, and that they are promising candidates for cell-based therapies for articular cartilage defects.

          Authors’ Affiliations

          (1)
          Department of Orthopaedic Surgery, The University of Tokyo

          Copyright

          © BioMed Central Ltd 2003

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