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An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis
Osteoporosis and multiple sclerosis are highly prevalent diseases with limited treatment options. In light of these unmet medical needs, novel therapeutic approaches are urgently sought. Previously, the activation of the transmembrane receptor Plexin-B1 by its ligand semaphorin 4D (Sema4D) has been...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396414/ https://www.ncbi.nlm.nih.gov/pubmed/35850304 http://dx.doi.org/10.1016/j.jbc.2022.102265 |
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author | Vogler, Melanie Oleksy, Arkadiusz Schulze, Sabrina Fedorova, Marina Kojonazarov, Baktybek Nijjar, Sharandip Patel, Seema Jossi, Sian Sawmynaden, Kovilen Henry, Maud Brown, Richard Matthews, David Offermanns, Stefan Worzfeld, Thomas |
author_facet | Vogler, Melanie Oleksy, Arkadiusz Schulze, Sabrina Fedorova, Marina Kojonazarov, Baktybek Nijjar, Sharandip Patel, Seema Jossi, Sian Sawmynaden, Kovilen Henry, Maud Brown, Richard Matthews, David Offermanns, Stefan Worzfeld, Thomas |
author_sort | Vogler, Melanie |
collection | PubMed |
description | Osteoporosis and multiple sclerosis are highly prevalent diseases with limited treatment options. In light of these unmet medical needs, novel therapeutic approaches are urgently sought. Previously, the activation of the transmembrane receptor Plexin-B1 by its ligand semaphorin 4D (Sema4D) has been shown to suppress bone formation and promote neuroinflammation in mice. However, it is unclear whether inhibition of this receptor–ligand interaction by an anti–Plexin-B1 antibody could represent a viable strategy against diseases related to these processes. Here, we raised and systematically characterized a monoclonal antibody directed against the extracellular domain of human Plexin-B1, which specifically blocks the binding of Sema4D to Plexin-B1. In vitro, we show that this antibody inhibits the suppressive effects of Sema4D on human osteoblast differentiation and mineralization. To test the therapeutic potential of the antibody in vivo, we generated a humanized mouse line, which expresses transgenic human Plexin-B1 instead of endogenous murine Plexin-B1. Employing these mice, we demonstrate that the anti–Plexin-B1 antibody exhibits beneficial effects in mouse models of postmenopausal osteoporosis and multiple sclerosis in vivo. In summary, our data identify an anti–Plexin-B1 antibody as a potential therapeutic agent for the treatment of osteoporosis and multiple sclerosis. |
format | Online Article Text |
id | pubmed-9396414 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-93964142022-08-25 An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis Vogler, Melanie Oleksy, Arkadiusz Schulze, Sabrina Fedorova, Marina Kojonazarov, Baktybek Nijjar, Sharandip Patel, Seema Jossi, Sian Sawmynaden, Kovilen Henry, Maud Brown, Richard Matthews, David Offermanns, Stefan Worzfeld, Thomas J Biol Chem Research Article Osteoporosis and multiple sclerosis are highly prevalent diseases with limited treatment options. In light of these unmet medical needs, novel therapeutic approaches are urgently sought. Previously, the activation of the transmembrane receptor Plexin-B1 by its ligand semaphorin 4D (Sema4D) has been shown to suppress bone formation and promote neuroinflammation in mice. However, it is unclear whether inhibition of this receptor–ligand interaction by an anti–Plexin-B1 antibody could represent a viable strategy against diseases related to these processes. Here, we raised and systematically characterized a monoclonal antibody directed against the extracellular domain of human Plexin-B1, which specifically blocks the binding of Sema4D to Plexin-B1. In vitro, we show that this antibody inhibits the suppressive effects of Sema4D on human osteoblast differentiation and mineralization. To test the therapeutic potential of the antibody in vivo, we generated a humanized mouse line, which expresses transgenic human Plexin-B1 instead of endogenous murine Plexin-B1. Employing these mice, we demonstrate that the anti–Plexin-B1 antibody exhibits beneficial effects in mouse models of postmenopausal osteoporosis and multiple sclerosis in vivo. In summary, our data identify an anti–Plexin-B1 antibody as a potential therapeutic agent for the treatment of osteoporosis and multiple sclerosis. American Society for Biochemistry and Molecular Biology 2022-07-15 /pmc/articles/PMC9396414/ /pubmed/35850304 http://dx.doi.org/10.1016/j.jbc.2022.102265 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Vogler, Melanie Oleksy, Arkadiusz Schulze, Sabrina Fedorova, Marina Kojonazarov, Baktybek Nijjar, Sharandip Patel, Seema Jossi, Sian Sawmynaden, Kovilen Henry, Maud Brown, Richard Matthews, David Offermanns, Stefan Worzfeld, Thomas An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title | An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title_full | An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title_fullStr | An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title_full_unstemmed | An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title_short | An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
title_sort | antagonistic monoclonal anti–plexin-b1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396414/ https://www.ncbi.nlm.nih.gov/pubmed/35850304 http://dx.doi.org/10.1016/j.jbc.2022.102265 |
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