Long-term effects of cyclic compressive loading on three-dimensionally cultured human synovium-derived cells

  • Muroi Yuri
    Graduate School of Dentistry (Oral and Maxillofacial Surgery), Osaka Dental University
  • Kakudo Kenji
    Second Department of Oral and maxillofacial Surgery, Osaka Dental University

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Cyclic mechanical stimuli on synovial cells have been implicated in pathogenesis of cartilage degradation and joint destruction, such as temporomandibular joint disease and rheumatoid arthritis. However, the precise mechanism of how tissue degradation is caused by cyclic mechanical loading has not been elucidated. Previously, we examined the short-term mechanical effects on matrix remodeling of three-dimensional (3 D) tissues containing human synovium-derived cells. However we did not examine the long-term effects. This study investigates the long-term effects of cyclic compressive loading on collagen-based engineered tissue containing human synovium-derived cells.<br> Human synovium-derived cells were seeded in a collagen scaffold made of atellocollagen (Koken, Tokyo, Japan) to construct 3 D engineered tissue. Unconfined axial compressive loading was applied for 5 or 15 days at 0, 5 or 20 kPa at 0.5 Hz for 1 hour/day using a custom-designed cyclic load bioreactor. We examine the histology and mRNA expression levels for MMP-1, MMP-3, TIMP-1, IL-8, SOX9, type II collagen and aggrecan. Three-dimensional deformation was also measured every 5 days during the mechanical loading.<br> Cell distribution and construction of the extracellular matrix were unaffected by mechanical loading at 5 and 20 kPa for 5 days. The collagen scaffold was fragmented only by loading at 20 kPa after 15 days. MMP-1, MMP-3, and IL-8 mRNA expression levels were up-regulated by the mechanical loading both at 5 and 15 days. Deformation of the 3D constructs significantly increased after 10 days at 20 kPa loading. This study showed that cyclic mechanical loading for longer period causes fragmentation of collagen-based 3D tissue with human synovium-derived cells, and that MMP-1 and MMP-3 might play a role in this process.

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