Effects of hexosamines and omega-3/omega-6 fatty acids on pH regulation by interleukin 1-treated isolated bovine articular chondrocytes.

Previous work has shown that interleukin 1 (IL-1) increases the activity of acid extruders in articular chondrocytes, while the H⁺-adenosine triphosphatase (ATPase) inhibitor bafilomycin can prevent aggrecanase-mediated cartilage degradation. The H⁺ transport induced by IL-1 may therefore be required for proteinase activity. In the present study, the effects of hexosamines and fish oils on H⁺-ATPase activity have been characterised for isolated bovine articular chondrocytes. Cells isolated in the presence of IL-1 were acidified, and the fraction of acid extrusion mediated by Na⁺–H⁺ exchange and an H⁺-ATPase were determined using specific inhibitors. Exposure to IL-1 significantly enhanced both components of acid extrusion. Co-incubation with glucosamine or mannosamine attenuated the H⁺-ATPase fraction of efflux. The addition of glucosamine at 9 h after exposure to IL-1—when H⁺-ATPase activation is already apparent—was also able to abolish H⁺-ATPase activity, implying that hexosamines do not exert effects at the level of protein synthesis. Co-incubation with the glucose transport inhibitor phloretin elicited similar effects to the hexosamines, suggesting that modulation of adenosine triphosphate levels may underlie their effects on H⁺-ATPase function. The omega-3 fish oil linolenic acid but not the omega-6 fish oil linoleic acid reduced H⁺-ATPase activity to levels seen in IL-1-untreated cells, although total efflux remained elevated, as a result of an enhanced H⁺ leak. These observations support a model whereby IL-1 stimulates an H⁺-ATPase-dependent system, possibly involved in aggrecanase activation, which appears to be one of the target mechanisms interrupted by dietary supplements reported to have symptom-modifying effects on osteoarthritis. [ABSTRACT FROM AUTHOR]

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