Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation
Dietary procyanidin has been shown to be an important bioactive component that regulates various pharmacological activities to maintain metabolic homeostasis. In particular, grape seed proanthocyanidin extract (GSPE) is a commercially available medicine for the treatment of venous and lymphatic dysf...
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MDPI AG
2020-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/10/3164 |
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| author | Sung Chul Kwak Yoon-Hee Cheon Chang Hoon Lee Hong Young Jun Kwon-Ha Yoon Myeung Su Lee Ju-Young Kim |
| author_facet | Sung Chul Kwak Yoon-Hee Cheon Chang Hoon Lee Hong Young Jun Kwon-Ha Yoon Myeung Su Lee Ju-Young Kim |
| author_sort | Sung Chul Kwak |
| collection | DOAJ |
| description | Dietary procyanidin has been shown to be an important bioactive component that regulates various pharmacological activities to maintain metabolic homeostasis. In particular, grape seed proanthocyanidin extract (GSPE) is a commercially available medicine for the treatment of venous and lymphatic dysfunction. This study aimed to investigate whether GSPE protects against lipopolysaccharide (LPS)-induced bone loss in vivo and the related mechanism of action in vitro. The administration of GSPE restored the inflammatory bone loss phenotype stimulated by acute systemic injection of LPS in vivo. GSPE strongly suppressed receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and bone resorption activity of mature osteoclasts by decreasing the RANKL-induced nuclear factor-κB transcription activity. GSPE mediates this effect through decreased phosphorylation and degradation of NF-κB inhibitor (IκB) by IκB kinaseβ, subsequently inhibiting proto-oncogene cellular Fos and nuclear factor of activated T cells. Additionally, GSPE promotes osteoclast proliferation by increasing the phosphorylation of components of the Akt and mitogen-activated protein kinase signaling pathways and it also inhibits apoptosis by decreasing the activity of caspase-8, caspase-9, and caspase-3, as corroborated by a decrease in the Terminal deoxynucleotidyl transferase dUTP nick end labeling -positive cells. Our study suggests a direct effect of GSPE on the proliferation, differentiation, and apoptosis of osteoclasts and reveals the mechanism responsible for the therapeutic potential of GSPE in osteoclast-associated bone metabolism disease. |
| first_indexed | 2024-03-10T15:34:08Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T15:34:08Z |
| publishDate | 2020-10-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-0352ed8d744c4b378b15e35db2bdb1f72023-11-20T17:20:50ZengMDPI AGNutrients2072-66432020-10-011210316410.3390/nu12103164Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and ProliferationSung Chul Kwak0Yoon-Hee Cheon1Chang Hoon Lee2Hong Young Jun3Kwon-Ha Yoon4Myeung Su Lee5Ju-Young Kim6Department of Anatomy, School of Medicine, Wonkwang University, Iksan 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan 54538, KoreaMedical Convergence Research Center, Wonkwang University Hospital, Iksan 54538, KoreaMedical Convergence Research Center, Wonkwang University Hospital, Iksan 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan 54538, KoreaDietary procyanidin has been shown to be an important bioactive component that regulates various pharmacological activities to maintain metabolic homeostasis. In particular, grape seed proanthocyanidin extract (GSPE) is a commercially available medicine for the treatment of venous and lymphatic dysfunction. This study aimed to investigate whether GSPE protects against lipopolysaccharide (LPS)-induced bone loss in vivo and the related mechanism of action in vitro. The administration of GSPE restored the inflammatory bone loss phenotype stimulated by acute systemic injection of LPS in vivo. GSPE strongly suppressed receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and bone resorption activity of mature osteoclasts by decreasing the RANKL-induced nuclear factor-κB transcription activity. GSPE mediates this effect through decreased phosphorylation and degradation of NF-κB inhibitor (IκB) by IκB kinaseβ, subsequently inhibiting proto-oncogene cellular Fos and nuclear factor of activated T cells. Additionally, GSPE promotes osteoclast proliferation by increasing the phosphorylation of components of the Akt and mitogen-activated protein kinase signaling pathways and it also inhibits apoptosis by decreasing the activity of caspase-8, caspase-9, and caspase-3, as corroborated by a decrease in the Terminal deoxynucleotidyl transferase dUTP nick end labeling -positive cells. Our study suggests a direct effect of GSPE on the proliferation, differentiation, and apoptosis of osteoclasts and reveals the mechanism responsible for the therapeutic potential of GSPE in osteoclast-associated bone metabolism disease.https://www.mdpi.com/2072-6643/12/10/3164grape seed proanthocyanidin extractosteoclastproliferationdifferentiationapoptosisbone disease |
| spellingShingle | Sung Chul Kwak Yoon-Hee Cheon Chang Hoon Lee Hong Young Jun Kwon-Ha Yoon Myeung Su Lee Ju-Young Kim Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation Nutrients grape seed proanthocyanidin extract osteoclast proliferation differentiation apoptosis bone disease |
| title | Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation |
| title_full | Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation |
| title_fullStr | Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation |
| title_full_unstemmed | Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation |
| title_short | Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation |
| title_sort | grape seed proanthocyanidin extract prevents bone loss via regulation of osteoclast differentiation apoptosis and proliferation |
| topic | grape seed proanthocyanidin extract osteoclast proliferation differentiation apoptosis bone disease |
| url | https://www.mdpi.com/2072-6643/12/10/3164 |
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