Therapeutic study, Level III.

No abstract

-Teriparatide, a therapeutic agent for osteoporosis, has been reported to increase the incidences of bone neoplasms such as osteosarcoma when administered subcutaneously to Fischer 344 (F344) rats for a long term, but its non-carcinogenic dose level following 2-year daily administration has not been established. Here we report detailed studies on the carcinogenicity of teriparatide following longterm administration. When teriparatide was administered subcutaneously to male and female SpragueDawley (SD) rats daily for 2 years, the incidence of osteosarcoma was increased at 13.6 μg/kg/day. The non-carcinogenic dose level was 4.5 μg/kg/day for both males and females. The development of osteosarcoma in SD rats depends on the dose level of, and treatment duration with, teriparatide. Responses of the bones to teriparatide were similar between F344 and SD rats in many aspects. These results suggested that the carcinogenic potential of teriparatide in SD rats is essentially the same as in F344 rats.

Retrospective cohort study, Level III.

The purpose of this study was to investigate the site-specific expression pattern and the role of chondrocyte clusters in human OA knee. Cartilage explants were obtained from 45 varus knees of medial and lateral femoral condyle undergoing total knee replacement surgery. Cartilage degeneration, number of chondrocytes, and the cell arrangement were evaluated by live/dead assay and immunohistochemical analyses with antibodies of STRO-1, FGF2, and Ki-67. Chondrocytes from medial and lateral femoral condyle were cultured to compare the potential of cell proliferation and production of cartilaginous nodules. Finally, cartilage tissue from medial femoral condyle, which included cartilage cleft with chondrocyte clusters, was observed the histological alternation. As the results, chondrocyte density adjacent to severe cartilage degeneration was highest, whereas chondrocytes in lateral femoral condyle displayed low density with single type of cells. Over 80% of these chondrocyte clusters were survived, expressing STRO-1, FGF2, and Ki-67. Furthermore, chondrocyte clusters proliferated faster and produced more cartilaginous nodules than single type of chondrocytes. Cartilage clefts involving numerous chondrocyte clusters were filled with extracellular matrix during organ culture. In conclusion, chondrocyte clusters adjacent to severe cartilage degeneration have shown completely specific characteristics with progenitor and proliferative potential. Regulating chondrocyte clusters may offer new approaches to cartilage repair and OA therapy in the future.

Background: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. The aetiology of RA remains unknown, but autoimmune responses are considered to play an important role in the disease pathophysiology. Currently available data suggests that the process of diagnosing RA may benefit from testing for anticyclic citrullinated peptides. Identification of the presence of citrullinated proteins in rheumatoid synovial fluids is important for the elucidation of the aetiology of RA as well as in the differential diagnosis of rheumatic-related diseases. Methods: A proteomics-based approach using electrophoresis/mass spectrometry was applied to identify the citrullinated proteins in synovial fluids from patients with RA. Synovial fluids from patients with RA were subjected to sodium dodecyl sulfate -polyacrylamide gel electrophoresis and Western blot analysis to detect the citrullinated proteins. Identification bands were then subjected to mass spectrometry. Results: Three proteins -citrullinated fibrinogen, citrullinated fibronectin and citrullinated vimentin -in synovial fluids from RA patients were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Conclusions: Proteomics-based analysis can be used to detect citrullinated proteins in synovial fluids from RA patients.

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