Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis

Autor: Anja Nohe, John Nguyen, Victoria Stone, Sean McTague, Daniel Halloran, Hilary W Durbano, Mark Eskander
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_treatment
Bone Morphogenetic Protein 2
SMAD
lcsh:Chemistry
0302 clinical medicine
Medicine
Casein Kinase II
Receptor
BMP signaling pathway
lcsh:QH301-705.5
Spectroscopy
Aged
80 and over
Osteoblast
General Medicine
Middle Aged
Computer Science Applications
medicine.anatomical_structure
030220 oncology & carcinogenesis
embryonic structures
Female
Casein kinase 2
Adult
animal structures
MAP Kinase Signaling System
CK2
BMP2
macromolecular substances
Bone morphogenetic protein 2
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Osteoclast
BMPRIa
Humans
Physical and Theoretical Chemistry
Molecular Biology
Bone Morphogenetic Protein Receptors
Type I
Aged
Osteoblasts
business.industry
Growth factor
Organic Chemistry
fungi
CK2.3
osteoporosis
030104 developmental biology
Gene Expression Regulation
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
business
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 18
International Journal of Molecular Sciences, Vol 21, Iss 6909, p 6909 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21186909
Popis: 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&rsquo
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.
Databáze: OpenAIRE
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