Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization
Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca<sup>2+</sup> and P<sub>i</sub>, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as a...
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2022-10-01
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author | Joanna Mroczek Slawomir Pikula Szymon Suski Lilianna Weremiejczyk Magdalena Biesaga Agnieszka Strzelecka-Kiliszek |
author_facet | Joanna Mroczek Slawomir Pikula Szymon Suski Lilianna Weremiejczyk Magdalena Biesaga Agnieszka Strzelecka-Kiliszek |
author_sort | Joanna Mroczek |
collection | DOAJ |
description | Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca<sup>2+</sup> and P<sub>i</sub>, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as annexins (Anx) and tissue-nonspecific alkaline phosphatase (TNAP), as well as low molecular-weight compounds. Apigenin, a flavonoid compound, has been reported to affect bone metabolism, but there are doubts about its mechanism of action under physiological and pathological conditions. In this report, apigenin potency to modulate annexin A6 (AnxA6)- and TNAP-mediated osteoblast mineralization was explored using three cell lines: human fetal osteoblastic hFOB 1.19, human osteosarcoma Saos-2, and human coronary artery smooth muscle cells HCASMC. We compared the mineralization competence, the morphology and composition of minerals, and the protein distribution in control and apigenin-treated cells and vesicles. The mineralization ability was monitored by AR-S/CPC analysis, and TNAP activity was determined by ELISA assay. Apigenin affected the mineral structure and modulated TNAP activity depending on the concentration. We also observed increased mineralization in Saos-2 cells. Based on TEM-EDX, we found that apigenin influenced the mineral composition. This flavonoid also disturbed the intracellular distribution of AnxA6 and TNAP, especially blocking AnxA6 aggregation and TNAP attachment to the membrane, as examined by FM analysis of cells and TEM-gold analysis of vesicles. In summary, apigenin modulates the mineralization process by regulating AnxA6 and TNAP, as well as through various effects on normal and cancer bone tissues or atherosclerotic soft tissue. |
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language | English |
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spelling | doaj.art-0a5bf675b0a447ff9f0ccc50dc0e321b2023-11-24T05:03:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211317910.3390/ijms232113179Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast MineralizationJoanna Mroczek0Slawomir Pikula1Szymon Suski2Lilianna Weremiejczyk3Magdalena Biesaga4Agnieszka Strzelecka-Kiliszek5Faculty of Chemistry, University of Warsaw, 1 Pasteur Str., 02-093 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, PolandFaculty of Chemistry, University of Warsaw, 1 Pasteur Str., 02-093 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, PolandMineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca<sup>2+</sup> and P<sub>i</sub>, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as annexins (Anx) and tissue-nonspecific alkaline phosphatase (TNAP), as well as low molecular-weight compounds. Apigenin, a flavonoid compound, has been reported to affect bone metabolism, but there are doubts about its mechanism of action under physiological and pathological conditions. In this report, apigenin potency to modulate annexin A6 (AnxA6)- and TNAP-mediated osteoblast mineralization was explored using three cell lines: human fetal osteoblastic hFOB 1.19, human osteosarcoma Saos-2, and human coronary artery smooth muscle cells HCASMC. We compared the mineralization competence, the morphology and composition of minerals, and the protein distribution in control and apigenin-treated cells and vesicles. The mineralization ability was monitored by AR-S/CPC analysis, and TNAP activity was determined by ELISA assay. Apigenin affected the mineral structure and modulated TNAP activity depending on the concentration. We also observed increased mineralization in Saos-2 cells. Based on TEM-EDX, we found that apigenin influenced the mineral composition. This flavonoid also disturbed the intracellular distribution of AnxA6 and TNAP, especially blocking AnxA6 aggregation and TNAP attachment to the membrane, as examined by FM analysis of cells and TEM-gold analysis of vesicles. In summary, apigenin modulates the mineralization process by regulating AnxA6 and TNAP, as well as through various effects on normal and cancer bone tissues or atherosclerotic soft tissue.https://www.mdpi.com/1422-0067/23/21/13179apigeninAnxA6TNAPmineralizationmatrix vesiclesosteoblast |
spellingShingle | Joanna Mroczek Slawomir Pikula Szymon Suski Lilianna Weremiejczyk Magdalena Biesaga Agnieszka Strzelecka-Kiliszek Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization International Journal of Molecular Sciences apigenin AnxA6 TNAP mineralization matrix vesicles osteoblast |
title | Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization |
title_full | Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization |
title_fullStr | Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization |
title_full_unstemmed | Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization |
title_short | Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization |
title_sort | apigenin modulates anxa6 and tnap mediated osteoblast mineralization |
topic | apigenin AnxA6 TNAP mineralization matrix vesicles osteoblast |
url | https://www.mdpi.com/1422-0067/23/21/13179 |
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