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...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6909 |
| _version_ | 1797553075225886720 |
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| author | Hilary W. Durbano Daniel Halloran John Nguyen Victoria Stone Sean McTague Mark Eskander Anja Nohe |
| author_facet | Hilary W. Durbano Daniel Halloran John Nguyen Victoria Stone Sean McTague Mark Eskander Anja Nohe |
| author_sort | Hilary W. Durbano |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T16:11:15Z |
| format | Article |
| id | doaj.art-0782d349398b4590aecff0c6f476cfa6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:11:15Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0782d349398b4590aecff0c6f476cfa62023-11-20T14:26:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118690910.3390/ijms21186909Aberrant BMP2 Signaling in Patients Diagnosed with OsteoporosisHilary W. Durbano0Daniel Halloran1John Nguyen2Victoria Stone3Sean McTague4Mark Eskander5Anja Nohe6Department of Biological Sciences, University of Delaware, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USAChristiana Care Hospital, Newark, DE 19716, USAChristiana Care Hospital, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USAThe 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.https://www.mdpi.com/1422-0067/21/18/6909osteoporosisBMP2CK2.3BMPRIaCK2 |
| spellingShingle | Hilary W. Durbano Daniel Halloran John Nguyen Victoria Stone Sean McTague Mark Eskander Anja Nohe Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis International Journal of Molecular Sciences osteoporosis BMP2 CK2.3 BMPRIa CK2 |
| 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 | osteoporosis BMP2 CK2.3 BMPRIa CK2 |
| url | https://www.mdpi.com/1422-0067/21/18/6909 |
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