Blue Mussel-Derived Peptides PIISVYWK and FSVVPSPK Trigger Wnt/β-Catenin Signaling-Mediated Osteogenesis in Human Bone Marrow Mesenchymal Stem Cells

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.

Plasma Spray vs. Electrochemical Deposition: Toward a Better Osteogenic Effect of Hydroxyapatite Coatings on 3D-Printed Titanium Scaffolds

“…We further detected the promotion effect of the coating on early and late osteogenic differentiation by ALP staining, alizarin red staining, and qRT-PCR. High expression of ALP is essential for the degradation of pyrophosphate in the early stage of osteogenic differentiation, an inhibitor of mineralization ( Jablonská et al, 2020 ; Oh et al, 2020 ; Tao et al, 2020 ; Chen et al, 2021b ). Therefore, rational morphology HA coatings and a low degree of crystalline formation of PS could enhance the osteogenic differentiation of BMSCs at the early stage.…”

Biological Functions of Let-7e-5p in Promoting the Differentiation of MC3T3-E1 Cells

“…The differentiation potential of osteoblasts is subject to various internal and external factors that are regulated by signaling pathways. These signaling pathways include the Wnt/β-catenin ( Oh et al, 2020 ; Park et al, 2020 ), MAPK ( Ge et al, 2007 ), and JAK/STAT ( Levy et al, 1996 ; Joung et al, 2012 , 2013 ; Darvin et al, 2013 ; Yu et al, 2018 ) pathways, which have all been reported to promote osteogenesis in vivo and in vitro . Furthermore, let-7 participates in the JAK2/STAT signaling pathway in cancer cells by targeting SOCS4 and activates the JAK1/STAT3 signaling pathway ( Patel et al, 2014 ; Chen et al, 2017 ).…”

“…Type I collagen, osteopontin ( OPN ), osteocalcin ( OCN ), and alkaline phosphatase (ALP) are secreted by cells and have important roles in osteoblast differentiation ( Long, 2011 ). In addition, several signaling pathways, including Wnt/β-catenin ( Oh et al, 2020 ; Park et al, 2020 ), MAPK ( Ge et al, 2007 ), and JAK/STAT ( Levy et al, 1996 ; Joung et al, 2012 , 2013 ; Darvin et al, 2013 ; Yu et al, 2018 ), promote osteogenesis in vivo and in vitro . Furthermore, the persistent activation of the JAK2/STAT5 signaling pathway increases osteoblastic differentiation ( Joung et al, 2012 , 2013 ; Darvin et al, 2013 ; Yu et al, 2018 ).…”

Cytoprotective Peptides from Blue Mussel Protein Hydrolysates: Identification and Mechanism Investigation in Human Umbilical Vein Endothelial Cells Injury

“…To date, many BAPs have been isolated and identified from marine dietary protein hydrolysates [27]. In addition, previous studies have identified specific BAPs in blue mussel protein hydrolysates that have been attributed antioxidant, antithrombotic, antihypertensive, osteogenic, and anti-osteoporotic effects [19,20,[28][29][30][31]. Blue mussel protein hydrolysate produced by α-chymotrypsin has been previously identified as a potential cytoprotective agent [1].…”