An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation
Less-calcaemic vitamin D receptor (VDR) agonists have the potential to promote osteoblast maturation in a bone regenerative setting. The emergence of lithocholic acid (LCA) as a bona fide VDR agonist holds promise as an adjunct for arthroplasty following reports that it was less calcaemic than calci...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/7/1113 |
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| author | Jason P. Mansell Aya Tanatani Hiroyuki Kagechika |
| author_facet | Jason P. Mansell Aya Tanatani Hiroyuki Kagechika |
| author_sort | Jason P. Mansell |
| collection | DOAJ |
| description | Less-calcaemic vitamin D receptor (VDR) agonists have the potential to promote osteoblast maturation in a bone regenerative setting. The emergence of lithocholic acid (LCA) as a bona fide VDR agonist holds promise as an adjunct for arthroplasty following reports that it was less calcaemic than calcitriol (1,25D). However, LCA and some earlier derivatives, e.g., LCA acetate, had to be used at much higher concentrations than 1,25D to elicit comparable effects on osteoblasts. However, recent developments have led to the generation of far more potent LCA derivatives that even outperform the efficacy of 1,25D. These new compounds include the cyanoamide derivative, Dcha-150 (also known as AY2-79). In light of this significant development, we sought to ascertain the ability of Dcha-150 to promote human osteoblast maturation by monitoring alkaline phosphatase (ALP) and osteocalcin (OC) expression. The treatment of MG63 cells with Dcha-150 led to the production of OC. When Dcha-150 was co-administered with lysophosphatidic acid (LPA) or an LPA analogue, a synergistic increase in ALP activity occurred, with Dcha-150 showing greater potency compared to 1,25D. We also provide evidence that this synergy is likely attributed to the actions of myocardin-related transcription factor (MRTF)–serum response factor (SRF) gene transcription following LPA-receptor-induced cytoskeletal reorganisation. |
| first_indexed | 2024-03-11T01:15:53Z |
| format | Article |
| id | doaj.art-b0a9fad3db564ed986003a948bf0b2ea |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T01:15:53Z |
| publishDate | 2023-07-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b0a9fad3db564ed986003a948bf0b2ea2023-11-18T18:31:37ZengMDPI AGBiomolecules2218-273X2023-07-01137111310.3390/biom13071113An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) DifferentiationJason P. Mansell0Aya Tanatani1Hiroyuki Kagechika2School of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UKDepartment of Chemistry, Faculty of Science, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610, JapanInstitute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Chiyoda-ku, Tokyo 101-0062, JapanLess-calcaemic vitamin D receptor (VDR) agonists have the potential to promote osteoblast maturation in a bone regenerative setting. The emergence of lithocholic acid (LCA) as a bona fide VDR agonist holds promise as an adjunct for arthroplasty following reports that it was less calcaemic than calcitriol (1,25D). However, LCA and some earlier derivatives, e.g., LCA acetate, had to be used at much higher concentrations than 1,25D to elicit comparable effects on osteoblasts. However, recent developments have led to the generation of far more potent LCA derivatives that even outperform the efficacy of 1,25D. These new compounds include the cyanoamide derivative, Dcha-150 (also known as AY2-79). In light of this significant development, we sought to ascertain the ability of Dcha-150 to promote human osteoblast maturation by monitoring alkaline phosphatase (ALP) and osteocalcin (OC) expression. The treatment of MG63 cells with Dcha-150 led to the production of OC. When Dcha-150 was co-administered with lysophosphatidic acid (LPA) or an LPA analogue, a synergistic increase in ALP activity occurred, with Dcha-150 showing greater potency compared to 1,25D. We also provide evidence that this synergy is likely attributed to the actions of myocardin-related transcription factor (MRTF)–serum response factor (SRF) gene transcription following LPA-receptor-induced cytoskeletal reorganisation.https://www.mdpi.com/2218-273X/13/7/1113osteoblastsdifferentiationlithocholic acidalkaline phosphatasemyocardin-related transcription factorserum response factor |
| spellingShingle | Jason P. Mansell Aya Tanatani Hiroyuki Kagechika An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation Biomolecules osteoblasts differentiation lithocholic acid alkaline phosphatase myocardin-related transcription factor serum response factor |
| title | An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation |
| title_full | An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation |
| title_fullStr | An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation |
| title_full_unstemmed | An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation |
| title_short | An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation |
| title_sort | n cyanoamide derivative of lithocholic acid co operates with lysophosphatidic acid to promote human osteoblast mg63 differentiation |
| topic | osteoblasts differentiation lithocholic acid alkaline phosphatase myocardin-related transcription factor serum response factor |
| url | https://www.mdpi.com/2218-273X/13/7/1113 |
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