No abstract

TGF beta-1 has been shown to upregulate matrix synthesis in articular chondrocytes. TGF beta-gene transfer to chondrocytes has the potential to increase the local production of this key component within regenerating cartilage after trauma and could support the repair process in articular cartilage lesions. Primary rabbit articular chondrocytes were cultured and retrovirally transfected with the experimental TGF beta-1 and the lacZ marker gene for control purposes. After radioactive labeling of new synthesized matrix proteins results were compared with normal primary chondrocytes. After TGF beta-1 gene transfer the endogenous growth factor concentration was doubled compared to normal chondrocytes and decreased in the lacZ control group. The proteoglycan synthesis in TGF beta-1 transfected chondrocytes showed a 96% increase compared to the basal production of normal chondrocytes. The LacZ transfected group revealed the opposite effect by a 44% decrease. The collagen synthesis of TGF beta-1 transfected chondrocytes was 304% compared to normal chondrocytes, predominantly type II collagen. The lacZ group collagen production was reduced by 35%. We conclude that TGF beta-1 gene transfer overcomes the decreasing effect observed by transfection with the LacZ marker gene and increases matrix synthesis in articular chondrocytes. Genetically altered chondrocytes might improve the repair of cartilage lesions by stimulating matrix synthesis and supporting the expression of the hyaline phenotype.

Immunologic prevention of the carcinogenicity of the diagnostic gamma-emitting radionuclide 99mTechnetium (99mTc) by lymphotoxin was evaluated using an in vivo-in vitro assay of carcinogenesis. Pregnant Syrian golden hamsters received 125-2,300 microCi 99mTc/kg body weight by injection, and 7 days later colonies of morphologically transformed cells were quantitated in vitro. The transformation frequency increased directly with the radionuclide concentration, and cells derived from transformed colonies produced tumors in athymic nude mice. The total absorbed 99mTc dose was 0.20 rad following injection of 250 microCi 99mTc/kg hamster body weight; this compares with an exposure of 0.13 rad following injection of 143 microCi 99mTc/kg body weight in humans. Intravenous injection of purified hamster lymphotoxin immediately after 99mTc caused a dose-dependent reduction in the transformation frequency. Transformation was essentially completely prevented (97%) by injection of 8,000 U of lymphotoxin. Thus, the immune system, through the action of lymphotoxin, has the potential to prevent carcinogenesis induced by gamma-radiation from 99mTc. This emphasizes the importance of considering the recipient's immune and other homeostatic mechanisms as part of a complete diagnostic or therapeutic gamma-radiation regimen.

Cytokines of rabbit synovial origin were injected into 6 rats under the epineurium of the sciatic nerve. Five controls were injected with similar preparations lacking cytokines. After injection, rats were examined for a period of 7 days. For neurophysiological evaluation the tibial branch of the sciatic nerve was stimulated with supramaximal voltage impulses of constant duration. The responses were recorded at the dorsal root entry zone L1. F-wave latencies were recorded at the distal hind paw after stimulation of the tibial nerve. Filters were set at LF: 20 Hz, HF: 10 kHz. Synovial cytokines caused a significant decrease in amplitude and increase in latencies of the recorded nerve potentials. Our results indicate that interleukin-1, which is a major component of the synovial cytokine preparation, could play an important role in degenerative spine disease through a damaging effect on nerve function. This action would explain why radiculopathy and pain can develop without signs of nerve compression. The results are also relevant to patients suffering from osteoarthritis and rheumatoid arthritis.