Biologically active peptides in milk
proteins can be used as effective
dietary supplements for management of bone-associated issues including
osteoporosis. A bioactive peptide derived from milk, viz. VLPVPQK/PepC,
has been validated previously from our lab for its osteoanabolic action.
In this study, we report 14 novel variants of PepC, designed in silico,
based on the structure–activity relationship, aiming to enhance
its osteogenic effect that holds tremendous therapeutic utility for
bone-related injuries. PepC was computationally modified at seven
positions of its original sequence, resulting in 14 modified synthetic
peptides for functional predictions and in vitro assessment by comparative
analysis of modified peptides by PepC for improved ability in osteogenic
functional assays (proliferation potential, antioxidant ability, gene
and protein expression, cytotoxic effect, bone mineralization) using
calvarial osteoblasts. For most peptides with the highest Peptide7
response relative to PepC (p < 0.05), enhanced
osteoanabolic response was observed. Further observations on Peptide7
have therefore been investigated in depth (qPCR, immunoblotting, LCMS/MS,
and PCA analysis). Peptide7 displayed a rise in the expression of
osteogenes (Osterix, Opg, Bmp2, and Runx2, p <
0.05) and protein (Runx2 and Bmp2, p < 0.05).
Besides, LCMS/MS findings suggest Peptide7 escapes intestinal peptidases
degradation. Experimental evidence supports an improved osteological
reaction to newly modified peptides and hence exploitation in the
preparation of functional foods or supplements.
Glucocorticoids exhibit a crucial role in the early onset of osteopenia. Milk and milk products have a beneficial influence on bone functioning. The study delineates the bone anabolic potential of three distinct milk varieties (goat, buffalo and cow) in reinstating the detrimental effects of dexamethasone (dex) in the mice models. The current findings report the prominent suppression in the glucocorticoid-induced bone loss on feeding goat, buffalo and cow milk in mice. Interestingly, goat milk showed maximum relative reversal of dex-driven bone loss. Hence, the study advocates the applied utility of milk and its exploitation in functional foods for the efficient check against glucocorticoidmediated bone loss.
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