title: Osteoclast-like cells in an in vitro model of bone destruction by rheumatoid synovium.
abstract: OBJECTIVE
  Osteoclasts may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers.
  
  
  METHODS
  Synovial tissues were obtained from rheumatoid arthritis and osteoarthritis patients and tissue pieces of about 2 mm(3) that contained synovial lining were cultured. Multinucleated cells derived from cultured synovial tissues were studied cytochemically and morphologically for osteoclast-specific markers.
  
  
  RESULTS
  Fibroblast-like and macrophage-like cells from the tissue pieces proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar H(+)-ATPase, the vitronectin receptor and cathepsin K. Although binding of (125)I-labelled salmon calcitonin was very low, the cells contained ringed structures of F-actin and showed strong bone-resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis.
  
  
  CONCLUSIONS
  Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.
authors: Department of Rheumatology, St Marianna University School of Medicine, Kawasaki, Japan.
authors: Y
authors: Y
authors: Suzuki
authors: Y
authors: Y
authors: Tsutsumi
authors: M
authors: M
authors: Nakagawa
authors: H
authors: H
authors: Suzuki
authors: K
authors: K
authors: Matsushita
authors: M
authors: M
authors: Beppu
authors: H
authors: H
authors: Aoki
authors: Y
authors: Y
authors: Ichikawa
authors: Y
authors: Y
authors: Mizushima
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000473:pathology; D001847:Bone Diseases / Q000209:etiology* / Q000473:pathology; D002116:Calcitonin / Q000096:biosynthesis; D005260:Female; D015726:Giant Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000473:pathology; D010010:Osteoclasts / Q000276:immunology* / Q000648:ultrastructure; D013583:Synovial Membrane / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: D000199:Actins; D002116:Calcitonin