Additional Evidence for Transthyretin Amyloid to Contribute to Osteoarthritis

The objective of this study was to investigate the role of TTR in vivo in mice transgenic for 90-100 copies of the wild-type human TTR (hTTR-TG mice) using an experimental OA and aging model. We used mice with transgenic overexpression of human rather than mouse TTR as the mouse protein is kinetically several orders of magnitude more stable than the human protein and hence is not subject to amyloid formation, which depends on tetramer dissociation. The hTTR-TG mouse strain that we have studied showed human TTR deposits between 12 and 17 months of age in the kidneys and heart. In mice over 18 months of age, TTR-related deposits were found in 84% in the kidneys and 39% in the heart. The main observation from the present study is that hTTR-TG mice develop more severe cartilage damage and synovitis than wild-type mice in the surgically induced OA model and aging model. This suggests that OA-related cartilage changes promote TTR deposition, which, in turn, seems to amplify the OA damage. The hTTR-TG mice did not present abnormalities in skeletal development and there were no differences in joint pathology compared to wild-type mice by 12 months. However, at 18 months, hTTR-TG mice developed significantly increased OA degeneration and synovial changes compared to wild-type. One of the main mechanisms of TTR amyloid pathogenesis is cytotoxicity. We showed that amyloidogenic TTR-induced cell death in cultured chondrocytes and one of the histological features of the hTTR...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs