Sanusi Bello Mada

Akt drives buffalo casein-derived novel peptide-mediated osteoblast differentiation

Milk is a potential nutraceutical with wide range of bioactive compounds that are antioxidative, antimicrobial, antithrombotic, immunomodulatory, opioid and antihypertensive. Various intervention studies with milk reflect its stupendous role in elevating bone mineral density. Milk and milk products have shown a preventive effect in bone loss during pre- and postmenopausal women. Since, milk is proved to have a vital role in bone health promotion, there is a need to identify bioactive compounds within it. Recently we have reported four novel peptides from milk casein for their osteoblast proliferation activity. Their role in differentiation and the signaling cascade evoked by them have not been studied. Thus, the present study has been designed to investigate the differentiation potential and signaling cascade of one of the novel peptides, that is, NAVPITPTL by analyzing osteoblast differentiation markers such as alkaline phosphatase activity, osteocalcin and mineral deposition. All the experimentations suggested a significant role of this peptide in osteoblast differentiation. The inhibitor studies, immunocytochemistry and immunoblotting have proven that the peptide-induced differentiation through pAkt signaling cascade as pAkt was observed in nucleus. Moreover, the peptide was found to be bioaccessible up to 1%.

Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide-induced dysfunction and cellular oxidative damage in rat osteoblastic cells.

Oxidative stress inhibits osteoblast differentiation and function that lead to the development of osteoporosis. Casein-derived peptide VLPVPQK (PEP), a potent antioxidant, was isolated from β-casein of buffalo milk. We used an in vitro oxidative stress model induced by hydrogen peroxide (H2O2) in rat osteoblastic cells to investigate the protective effects of PEP against H2O2-induced dysfunction and oxidative damage. Cells were pretreated with PEP (50–200 ng/mL) for 2, 7 or 21 days followed by 0.3 mM H2O2 treatment for 24 h and then markers of osteogenic development, oxidative damage and apoptosis were examined. PEP significantly increased the viability and differentiation markers of osteoblast cells such as alkaline phosphatase and calcium mineralization. Moreover, PEP suppressed the production of reactive oxygen species (ROS), lipid peroxidation and ameliorated H2O2-induced reduction in glutathione, superoxide dismutase and catalase activities. In addition, PEP partially inhibited caspase-9 and-3 activities and reduced propidium iodide–positive cells. Altogether, our results demonstrated that PEP could protect rat osteoblast against H2O2-induced dysfunction and oxidative damage by reduction of ROS production, lipid peroxidation and increased antioxidant enzyme activities. Thus, our data suggest that PEP might be a valuable protective agent against oxidative stress–related diseases such as osteoporosis.

Postmenopausal osteoporosis and breast cancer: The biochemical links and beneficial effects of functional foods

Breast cancer as a multifactorial disease has been classified among the major causes of morbidity and mortality in women across the world, with a higher prevalence among post-menopausal women. Osteoporosis, a condition characterized by altered bone mineralization is also commonly found among post-menopausal women. Consequently, post-menopausal women are at risk of morbidity and mortality associated with breast cancer and postmenopausal osteoporosis. This may not be unconnected to the fact that, there may be existent biochemical links between the two mayhems, which might rally round between the cellular and molecular connectivity based on the actions and inactions of RANKL, estrogen, free radicals-induced oxidative stress and metabolic implications of age related obesity among others. Cells and tissues including breast and bone are more prone to oxidative stress with age, and oxidative stress could alter the activity of key proteins and pathways required for protection against breast cancer and osteoporosis. As a result, the potentials of antioxidant rich functional foods in preventing, managing and possibly treating breast cancer and postmenopausal osteoporosis cannot be overemphasised. This review mainly uses ISI, SCOPUS and PubMed indexed journals and books containing various experimental reports vacillating from humans, animals and in vitro studies in relation to breast cancer and postmenopausal osteoporosis, biochemical links and possible beneficial effects of functional foods. One distinct feature of the review is that it categorically intends to provide a critical appraisal on the said available experimental data within the variables of breast cancer and osteoporosis among females vis-à-vis the potentials of functional foods.