RESUMO
Milk contains various bioactive components with osteoanabolic properties. This study investigates the comparative effect of the whey-derived antioxidative (YVEEL) and angiotensin-converting enzyme inhibitory (YLLF) bioactive peptides on bone remodelling in ovariectomised (OVX) osteoporotic rat model. OVX animals were administered with antioxidative (AO) (500 µg kg-1 day-1) and angiotensin-converting enzyme inhibitory (ACE inhibitory) (50 µg kg-1 day-1) peptides for eight weeks. Trabecular microarchitectural parameters of femoral and tibiae bone were determined using micro-CT scan. Bone formation, resorption, turnover markers (ALP, RANKL, OCN) and inflammatory cytokines (TNF-α, TGF-ß, IFN-γ) were determined by ELISA. Both AO and ACE inhibitory peptides inhibited the increase in bone turnover and inflammatory cytokines while increased the bone formation markers. The altered morphometric parameters of femoral and tibiae bones due to OVX were strikingly attenuated by the peptide administration. The results indicated that AO peptide exerts more osteoprotective potential than ACE inhibitory peptide by suppressing inflammatory status and enhancing bone formation markers.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Suplementos Nutricionais , Oligopeptídeos/uso terapêutico , Osteoporose Pós-Menopausa/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Proteínas do Soro do Leite/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides , Antioxidantes/química , Antioxidantes/uso terapêutico , Biomarcadores/sangue , Conservadores da Densidade Óssea/química , Remodelação Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/imunologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/imunologia , Feminino , Humanos , Mediadores da Inflamação/sangue , Oligopeptídeos/química , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/imunologia , Ovariectomia/efeitos adversos , Fragmentos de Peptídeos/química , Distribuição Aleatória , Ratos Wistar , Tomografia Computadorizada por Raios X , Proteínas do Soro do Leite/químicaRESUMO
Exploring bone rebuilding anabolic agents has been gaining much attention due to their potential therapeutic effects in treating several bone disorders including osteoporosis. Whey protein has been reported to affect bone health osteoanabolically, in terms of proliferation and differentiation of primary osteoblast cells. This study investigates whether whey derived anti-oxidative (AO) (P1- MHIRL, P2- YVEEL) and angiotensin converting enzyme inhibitory (ACE inhibitory) (P3- YLLF, P4-ALPMHIR, P5-IPA, P6- WLAHK) bioactive peptides affect the proliferation and differentiation of primary osteoblast cells isolated from rat calvaria. The proliferation and osteogenic activity of osteoblast cells in presence of these peptides were determined by MTT assay, DNA quantification study, Alkaline phosphatase activity (ALP) and ALP staining, Alizarin red activity and staining, and secretory osteocalcin measurement. The expression of osteogenesis-related genes (COLI-α, ALP, OCN and RUNX2) were determined by real-time quantitative PCR (RT-PCR) analysis over a period of 21days. The peptide treated osteoblasts showed a significant increase in viable cell density and proliferation in the order of P2>P6>P3 at optimised concentration. Furthermore, the osteoblastic differentiation markers in response to these peptides were found to be significantly up regulated in the order of P2>P6>P3 when compared to the controls. These results demonstrated that bioactive whey-derived AO and ACE inhibitory peptides can play a potential therapeutic role in osteoporosis by activating osteoblasts anabolically.
