Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Durbano, Hilary W., Halloran, Daniel, Nguyen, John, Stone, Victoria, McTague, Sean, Eskander, Mark, Nohe, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783593954547073024
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
work_keys_str_mv AT durbanohilaryw aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT hallorandaniel aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT nguyenjohn aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT stonevictoria aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT mctaguesean aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT eskandermark aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis
AT noheanja aberrantbmp2signalinginpatientsdiagnosedwithosteoporosis