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Open AccessArticle

Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation

1
Department of Anatomy, School of Medicine, Wonkwang University, Iksan 54538, Korea
2
Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan 54538, Korea
3
Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, Iksan 54538, Korea
4
Medical Convergence Research Center, Wonkwang University Hospital, Iksan 54538, Korea
5
Department of Radiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(10), 3164; https://doi.org/10.3390/nu12103164
Received: 15 September 2020 / Revised: 12 October 2020 / Accepted: 14 October 2020 / Published: 16 October 2020
(This article belongs to the Section Phytochemicals and Human Health)
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. View Full-Text
Keywords: grape seed proanthocyanidin extract; osteoclast; proliferation; differentiation; apoptosis; bone disease grape seed proanthocyanidin extract; osteoclast; proliferation; differentiation; apoptosis; bone disease
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Kwak, S.C.; Cheon, Y.-H.; Lee, C.H.; Jun, H.Y.; Yoon, K.-H.; Lee, M.S.; Kim, J.-Y. Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation. Nutrients 2020, 12, 3164.

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