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Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis
The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-de...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555210/ https://www.ncbi.nlm.nih.gov/pubmed/32967078 http://dx.doi.org/10.3390/ijms21186909 |
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author | Durbano, Hilary W. Halloran, Daniel Nguyen, John Stone, Victoria McTague, Sean Eskander, Mark Nohe, Anja |
author_facet | Durbano, Hilary W. Halloran, Daniel Nguyen, John Stone, Victoria McTague, Sean Eskander, Mark Nohe, Anja |
author_sort | Durbano, Hilary W. |
collection | PubMed |
description | The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-dependent and SMAD-independent signaling. A novel interaction between the BMP type Ia receptor (BMPRIa) and casein kinase II (CK2) was discovered, and several CK2 phosphorylation sites were identified. A corresponding blocking peptide (named CK2.3) was designed to further elucidate the phosphorylation site’s function. Previously, CK2.3 demonstrated an increased osteoblast activity and decreased osteoclast activity in a variety of animal models, cell lines, and isolated human osteoblasts. It is hypothesized that CK2.3 completes these actions through the BMP signaling pathway. Furthermore, it was recently discovered that BMP2 did not elicit an osteogenic response in osteoblasts from patients diagnosed with OP, while CK2.3 did. In this study, we explore where in the BMP pathway the signaling disparity or defect lies in those diagnosed with OP. We found that osteoblasts isolated from patients diagnosed with OP did not activate SMAD or ERK signaling after BMP2 stimulation. When OP osteoblasts were stimulated with BMP2, both BMPRIa and CK2 expression significantly decreased. This indicates a major disparity within the BMP signaling pathway in patients diagnosed with osteoporosis. |
format | Online Article Text |
id | pubmed-7555210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75552102020-10-19 Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis Durbano, Hilary W. Halloran, Daniel Nguyen, John Stone, Victoria McTague, Sean Eskander, Mark Nohe, Anja Int J Mol Sci Article The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-dependent and SMAD-independent signaling. A novel interaction between the BMP type Ia receptor (BMPRIa) and casein kinase II (CK2) was discovered, and several CK2 phosphorylation sites were identified. A corresponding blocking peptide (named CK2.3) was designed to further elucidate the phosphorylation site’s function. Previously, CK2.3 demonstrated an increased osteoblast activity and decreased osteoclast activity in a variety of animal models, cell lines, and isolated human osteoblasts. It is hypothesized that CK2.3 completes these actions through the BMP signaling pathway. Furthermore, it was recently discovered that BMP2 did not elicit an osteogenic response in osteoblasts from patients diagnosed with OP, while CK2.3 did. In this study, we explore where in the BMP pathway the signaling disparity or defect lies in those diagnosed with OP. We found that osteoblasts isolated from patients diagnosed with OP did not activate SMAD or ERK signaling after BMP2 stimulation. When OP osteoblasts were stimulated with BMP2, both BMPRIa and CK2 expression significantly decreased. This indicates a major disparity within the BMP signaling pathway in patients diagnosed with osteoporosis. MDPI 2020-09-21 /pmc/articles/PMC7555210/ /pubmed/32967078 http://dx.doi.org/10.3390/ijms21186909 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Durbano, Hilary W. Halloran, Daniel Nguyen, John Stone, Victoria McTague, Sean Eskander, Mark Nohe, Anja Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title | Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title_full | Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title_fullStr | Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title_full_unstemmed | Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title_short | Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis |
title_sort | aberrant bmp2 signaling in patients diagnosed with osteoporosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555210/ https://www.ncbi.nlm.nih.gov/pubmed/32967078 http://dx.doi.org/10.3390/ijms21186909 |
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