Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo.

There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

Hyperthermia for the treatment of articular cartilage with osteoarthritis.

Osteoarthritis (OA) is one of the most frequent musculoskeletal disorders in the elderly population. OA is characterised by a gradual loss of extracellular matrix in the articular cartilage of joints. OA can only be managed by artificial joint replacement when joint destruction becomes severe. Therefore, it is preferable to administer conservative therapy that is easy, simple and effective in inhibiting OA progression at the early stage. Heat shock protein 70 (Hsp70) has a protective effect on the cartilage and inhibits the apoptosis of chondrocytes. Heat stimulation by microwave to the joints can increase Hsp70 expression in chondrocytes, and at the same time, Hsp70 expression partially enhances matrix metabolism of the cartilage. These findings suggest that hyperthermia can be positively applied to the treatment of OA. Hyperthermia is therefore expected to be an inexpensive and less-invasive conservative therapy for OA.

The effect of apoptosis signal-regulating kinase 1 gene transfer on rat collagen induced arthritis.

OBJECTIVE: To examine the apoptosis-inducing effect of apoptosis signal-regulating kinase 1 (ASK1) gene transfer into synovial cells in vitro and in vivo. METHODS: An adenovirus vector was constructed so that a constitutively active form of ASK1 gene (ASK1DeltaN) was expressed in the presence of the Cre recombinase. The ASK1DeltaN and Cre adenovirus vectors were cotransduced into cultured synoviocytes derived from patients with rheumatoid arthritis (RA), and apoptosis was evaluated by TUNEL and Hoechst staining. Collagen induced arthritis (CIA) was induced in 8-week-old male DA rats, and 10 days later the 2 adenovirus vectors were coadministered into the ankle joints of the animals. As indicators of severity of arthritis, swelling of the ankle and articular index (AI) scores were evaluated, while histopathological observation of articular tissue was also performed. RESULTS: In the cultured human RA synoviocytes, overexpression of the ASK1DeltaN significantly reduced cell viability and induced apoptosis. In the CIA rats transduced with the ASK1DeltaN gene, arthritis was significantly promoted in terms of the swelling of the ankle joints and elevation of the AI scores. Histopathological observation also revealed that the constitutively active ASK1 induced massive infiltration of inflammatory cells into the synovial membrane as well as proliferation of synovial fibroblasts. Degeneration of the synovial membrane was not evident. CONCLUSION: Adenoviral transduction of ASK1DeltaN induced apoptosis in RA synoviocytes in vitro, but not in CIA synovium in vivo.