Abstract
Marine-derived bioactive peptides have shown potential bone health promoting effects. Although various marine-derived bioactive peptides have potential nutraceutical or pharmaceutical properties, only a few of them are commercially available. This study presented an osteogenic mechanism of blue mussel-derived peptides PIISVYWK and FSVVPSPK as potential bone health promoting agents in human bone marrow-derived mesenchymal stem cells (hBMMSCs). Alkaline phosphatase (ALP) activity and mineralization were stimulated using PIISVYWK and FSVVPSPK as early and late markers of osteogenesis in a concentration-dependent manner. Western blot and RT-qPCR results revealed that PIISVYWK and FSVVPSPK increased osteoblast differentiation of hBMMSCs by activating canonical Wnt/β-catenin signaling-related proteins and mRNAs. Immunofluorescence images confirmed nuclear translocation of β-catenin in osteogenic differentiation. Treatment with the pharmacological inhibitor DKK-1 blocked PIISVYWK- and FSVVPSPK-induced ALP activity and mineralization, as well as mRNA expression of the canonical Wnt/β-catenin signaling pathway in hBMMSC differentiation into osteoblasts. These findings suggested that PIISVYWK and FSVVPSPK promoted the canonical Wnt/β-catenin signaling pathway in osteogenesis of hBMMSCs. Blue mussel-derived PIISVYWK and FSVVPSPK might help develop peptide-based therapeutic agents for bone-related diseases.
Highlights
Osteoporosis is one of the most common diseases caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts
Alkaline phosphatase (ALP) activity and mineralization, as well as mRNA expression of the canonical Wnt/β-catenin signaling pathway in human bone marrow-derived mesenchymal stem cells (hBMMSCs) differentiation into osteoblasts. These findings suggested that PIISVYWK and FSVVPSPK promoted the canonical Wnt/β-catenin signaling pathway in osteogenesis of hBMMSCs
On hBMMSC differentiation into osteoblasts, hBMMSCs were treated with osteogenic medium (OM)
Summary
Osteoporosis is one of the most common diseases caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. The aging population is more prone to osteoporosis as a result of bone resorption rates being higher than bone formation rates [1]. The main classes of these agents are bisphosphonates, calcium, and estrogen, and they help maintain bone mass by inhibiting osteoclasts [2]. A number of bone-forming agents, derived from natural products, have been developed to treat osteoporosis by enhancing mesenchymal stem cell (MSC) differentiation into osteoblasts [4,5,6,7]. MSCs can differentiate into osteogenic, chondrogenic, and adipogenic lineage cells [8].
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