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Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization

The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals....

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Autores principales: Na, Woojin, Kang, Min-Kyung, Park, Sin-Hye, Kim, Dong Yeon, Oh, Su Yeon, Oh, Moon-Sik, Park, Sohyun, Kang, II-Jun, Kang, Young-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621655/
https://www.ncbi.nlm.nih.gov/pubmed/34830274
http://dx.doi.org/10.3390/ijms222212391
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author Na, Woojin
Kang, Min-Kyung
Park, Sin-Hye
Kim, Dong Yeon
Oh, Su Yeon
Oh, Moon-Sik
Park, Sohyun
Kang, II-Jun
Kang, Young-Hee
author_facet Na, Woojin
Kang, Min-Kyung
Park, Sin-Hye
Kim, Dong Yeon
Oh, Su Yeon
Oh, Moon-Sik
Park, Sohyun
Kang, II-Jun
Kang, Young-Hee
author_sort Na, Woojin
collection PubMed
description The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals. Considerable efforts have been made in developing naturally-occurring plant compounds, preventing bone pathologies, or enhancing bone regeneration. Coumarin aesculetin inhibits osteoporosis through hampering the ruffled border formation of mature osteoclasts. However, little is known regarding the effects of aesculetin on the impairment of matrix vesicle biogenesis. MC3T3-E1 cells were cultured in differentiation media with 1–10 μM aesculetin for up to 21 days. Aesculetin boosted the bone morphogenetic protein-2 expression, and alkaline phosphatase activation of differentiating MC3T3-E1 cells. The presence of aesculetin strengthened the expression of collagen type 1 and osteoprotegerin and transcription of Runt-related transcription factor 2 in differentiating osteoblasts for 9 days. When ≥1–5 μM aesculetin was added to differentiating cells for 15–18 days, the induction of non-collagenous proteins of bone sialoprotein II, osteopontin, osteocalcin, and osteonectin was markedly enhanced, facilitating the formation of hydroxyapatite crystals and mineralized collagen matrix. The induction of annexin V and PHOSPHO 1 was further augmented in ≥5 μM aesculetin-treated differentiating osteoblasts for 21 days. In addition, the levels of tissue-nonspecific alkaline phosphatase and collagen type 1 were further enhanced within the extracellular space and on matrix vesicles of mature osteoblasts treated with aesculetin, indicating matrix vesicle-mediated bone mineralization. Finally, aesculetin markedly accelerated the production of thrombospondin-1 and tenascin C in mature osteoblasts, leading to their adhesion to preformed collagen matrix. Therefore, aesculetin enhanced osteoblast differentiation, and matrix vesicle biogenesis and mineralization. These findings suggest that aesculetin may be a potential osteo-inductive agent preventing bone pathologies or enhancing bone regeneration.
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spelling pubmed-86216552021-11-27 Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization Na, Woojin Kang, Min-Kyung Park, Sin-Hye Kim, Dong Yeon Oh, Su Yeon Oh, Moon-Sik Park, Sohyun Kang, II-Jun Kang, Young-Hee Int J Mol Sci Article The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals. Considerable efforts have been made in developing naturally-occurring plant compounds, preventing bone pathologies, or enhancing bone regeneration. Coumarin aesculetin inhibits osteoporosis through hampering the ruffled border formation of mature osteoclasts. However, little is known regarding the effects of aesculetin on the impairment of matrix vesicle biogenesis. MC3T3-E1 cells were cultured in differentiation media with 1–10 μM aesculetin for up to 21 days. Aesculetin boosted the bone morphogenetic protein-2 expression, and alkaline phosphatase activation of differentiating MC3T3-E1 cells. The presence of aesculetin strengthened the expression of collagen type 1 and osteoprotegerin and transcription of Runt-related transcription factor 2 in differentiating osteoblasts for 9 days. When ≥1–5 μM aesculetin was added to differentiating cells for 15–18 days, the induction of non-collagenous proteins of bone sialoprotein II, osteopontin, osteocalcin, and osteonectin was markedly enhanced, facilitating the formation of hydroxyapatite crystals and mineralized collagen matrix. The induction of annexin V and PHOSPHO 1 was further augmented in ≥5 μM aesculetin-treated differentiating osteoblasts for 21 days. In addition, the levels of tissue-nonspecific alkaline phosphatase and collagen type 1 were further enhanced within the extracellular space and on matrix vesicles of mature osteoblasts treated with aesculetin, indicating matrix vesicle-mediated bone mineralization. Finally, aesculetin markedly accelerated the production of thrombospondin-1 and tenascin C in mature osteoblasts, leading to their adhesion to preformed collagen matrix. Therefore, aesculetin enhanced osteoblast differentiation, and matrix vesicle biogenesis and mineralization. These findings suggest that aesculetin may be a potential osteo-inductive agent preventing bone pathologies or enhancing bone regeneration. MDPI 2021-11-17 /pmc/articles/PMC8621655/ /pubmed/34830274 http://dx.doi.org/10.3390/ijms222212391 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Na, Woojin
Kang, Min-Kyung
Park, Sin-Hye
Kim, Dong Yeon
Oh, Su Yeon
Oh, Moon-Sik
Park, Sohyun
Kang, II-Jun
Kang, Young-Hee
Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_full Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_fullStr Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_full_unstemmed Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_short Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_sort aesculetin accelerates osteoblast differentiation and matrix-vesicle-mediated mineralization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621655/
https://www.ncbi.nlm.nih.gov/pubmed/34830274
http://dx.doi.org/10.3390/ijms222212391
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