Adipokine actions on cartilage homeostasis.

Epidemiological studies have shown an intriguing correlation between obesity and articular cartilage disease. An increase in mechanical forces across weight-bearing joints has long been considered the primary factor leading to joint degeneration. However, emerging data suggest that additional soluble factors such as the adipocyte-derived molecules "adipokines" may also play an important role in the onset and progression of weight-associated cartilage degradative process. Adipokines are pleiotropic secretory molecules mainly produced by white adipose tissue. Adipokines exert their actions through endocrine, paracrine, autocrine, or juxtacrine cross talk in a wide variety of physiological or pathophysiological processes. In particular, they are mainly involved in the regulation of food intake and energy metabolism, in both health and disease states, and in the inflammatory response. Recent observations have shown that, among adipokines, leptin, adiponectin, resistin, visfatin, and apelin may also participate to the complex mechanisms that regulate skeleton biology, both at bone and cartilage level. Herein, we review the present knowledge about the role of these adipokines in cartilage function as well as in inflammatory and degenerative joint diseases. Moreover, we describe some methodological approaches which can be utilized in the measurement of these adipokines in different biological matrices, like plasma and synovial fluid (SF), and may be helpful to better clarify the involvement of these molecules in cartilage disease.

The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells.

Unlike normal cells, tumor cells survive in a specific redox environment where the elevated reactive oxygen species contribute to enhance cell proliferation and to suppress apoptosis. Alpha-lipoic acid, a naturally occurring reactive oxygen species scavenger, has been shown to possess anticancer activity, due to its ability to suppress proliferation and to induce apoptosis in different cancer cell lines. Since at the moment little information is available regarding the potential effects of alpha-lipoic acid on breast cancer, in the present study we addressed the question whether alpha-lipoic acid induces cell cycle arrest and apoptosis in the human breast cancer cell line MCF-7. Moreover, we investigated some molecular mechanisms which mediate alpha-lipoic acid actions, focusing on the role of the PI3-K/Akt signalling pathway. We observed that alpha-lipoic acid is able to scavenge reactive oxygen species in MCF-7 cells and that the reduction of reactive oxygen species is followed by cell growth arrest in the G1 phase of the cell cycle, via the specific inhibition of Akt pathway and the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1), and by apoptosis, via changes of the ratio of the apoptotic-related protein Bax/Bcl-2. Thus, the anti-tumor activity of alpha-lipoic acid observed in MCF-7 cells further stresses the role of redox state in regulating cancer initiation and progression.