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:	Woojin Na, Min-Kyung Kang, Sin-Hye Park, Dong Yeon Kim, Su Yeon Oh, Moon-Sik Oh, Sohyun Park, II-Jun Kang, Young-Hee Kang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aesculetin collagen mineralization hydroxyapatite matrix vesicles non-collagenous proteins osteoblast differentiation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/96c2906b96344f758c60c048bff22d4b
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spelling	oai:doaj.org-article:96c2906b96344f758c60c048bff22d4b2021-11-25T17:56:13ZAesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization10.3390/ijms2222123911422-00671661-6596https://doaj.org/article/96c2906b96344f758c60c048bff22d4b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12391https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Woojin NaMin-Kyung KangSin-Hye ParkDong Yeon KimSu Yeon OhMoon-Sik OhSohyun ParkII-Jun KangYoung-Hee KangMDPI AGarticleaesculetincollagen mineralizationhydroxyapatitematrix vesiclesnon-collagenous proteinsosteoblast differentiationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12391, p 12391 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aesculetin collagen mineralization hydroxyapatite matrix vesicles non-collagenous proteins osteoblast differentiation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	aesculetin collagen mineralization hydroxyapatite matrix vesicles non-collagenous proteins osteoblast differentiation Biology (General) QH301-705.5 Chemistry QD1-999 Woojin Na Min-Kyung Kang Sin-Hye Park Dong Yeon Kim Su Yeon Oh Moon-Sik Oh Sohyun Park II-Jun Kang Young-Hee Kang Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
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.
format	article
author	Woojin Na Min-Kyung Kang Sin-Hye Park Dong Yeon Kim Su Yeon Oh Moon-Sik Oh Sohyun Park II-Jun Kang Young-Hee Kang
author_facet	Woojin Na Min-Kyung Kang Sin-Hye Park Dong Yeon Kim Su Yeon Oh Moon-Sik Oh Sohyun Park II-Jun Kang Young-Hee Kang
author_sort	Woojin Na
title	Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization
title_short	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_sort	aesculetin accelerates osteoblast differentiation and matrix-vesicle-mediated mineralization
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/96c2906b96344f758c60c048bff22d4b
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Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization

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