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贻贝源肽 PIISVYWK 和 FSVVPSPK 触发人骨髓间充质干细胞 Wnt/β-连环蛋白信号通路介导的成骨作用。

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

机构信息

Institute of Marine Life Sciences, Pukyong National University, Busan 48613, Korea.

Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Korea.

出版信息

Mar Drugs. 2020 Oct 9;18(10):510. doi: 10.3390/md18100510.

DOI:10.3390/md18100510
PMID:33050263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7599581/
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.

摘要

海洋来源的生物活性肽具有促进骨骼健康的潜力。虽然各种海洋来源的生物活性肽具有潜在的营养保健品或药物特性,但只有少数几种可商业化。本研究提出了贻贝来源的肽 PIISVYWK 和 FSVVPSPK 作为促进人类骨髓间充质干细胞(hBMMSCs)骨骼健康的潜在作用机制。PIISVYWK 和 FSVVPSPK 以浓度依赖的方式作为成骨早期和晚期的标记物,刺激碱性磷酸酶(ALP)活性和矿化。Western blot 和 RT-qPCR 结果表明,PIISVYWK 和 FSVVPSPK 通过激活经典 Wnt/β-连环蛋白信号相关蛋白和 mRNAs 增加 hBMMSCs 的成骨分化。免疫荧光图像证实了β-连环蛋白在成骨分化中的核转位。用药理学抑制剂 DKK-1 处理可阻断 PIISVYWK 和 FSVVPSPK 诱导的 ALP 活性和矿化,以及 hBMMSC 分化为成骨细胞过程中经典 Wnt/β-连环蛋白信号通路的 mRNA 表达。这些发现表明,PIISVYWK 和 FSVVPSPK 促进了 hBMMSCs 成骨过程中的经典 Wnt/β-连环蛋白信号通路。贻贝来源的 PIISVYWK 和 FSVVPSPK 可能有助于开发基于肽的治疗骨相关疾病的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac06/7599581/532f154140cc/marinedrugs-18-00510-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac06/7599581/532f154140cc/marinedrugs-18-00510-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac06/7599581/50e386c0ddaf/marinedrugs-18-00510-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac06/7599581/b518af8c770e/marinedrugs-18-00510-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac06/7599581/12b2d9ff3dc4/marinedrugs-18-00510-g003.jpg
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