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Open AccessArticle

Vitamin C Activates Osteoblastogenesis and Inhibits Osteoclastogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways

Department of Food and Nutrition, KC University, Seoul 077661, Korea
Department of Food Science and Technology, Seoul National University of Science & Technology, Seoul 01811, Korea
Department of Biomedical Engineering, Sogang University, Seoul 04107, Korea
Department of Advanced Materials Engineering, Daejeon University, Daejeon 34520, Korea
Kwang-Dong Pharmaceutical Co, Ltd., Seoul 06650, Korea
Author to whom correspondence should be addressed.
Nutrients 2019, 11(3), 506;
Received: 23 January 2019 / Revised: 22 February 2019 / Accepted: 25 February 2019 / Published: 27 February 2019
(This article belongs to the Special Issue Nutritional Status and Bone Health)
This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/β-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration. View Full-Text
Keywords: Vitamin C; osteoblasts; osteoclasts; osteoporosis; ovariectomized rats Vitamin C; osteoblasts; osteoclasts; osteoporosis; ovariectomized rats
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Choi, H.K.; Kim, G.-J.; Yoo, H.-S.; Song, D.H.; Chung, K.-H.; Lee, K.-J.; Koo, Y.T.; An, J.H. Vitamin C Activates Osteoblastogenesis and Inhibits Osteoclastogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways. Nutrients 2019, 11, 506.

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