CK2.3, a Mimetic Peptide of the BMP Type I Receptor, Increases Activity in Osteoblasts over BMP2

Autor: Debra Dibert, Mark Eskander, Hilary Weidner, Victor Yuan Gao, Sean McTague, Liyun Wang, Anja Nohe, Randall L. Duncan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Bone disease
Osteoporosis
Bone Morphogenetic Protein 2
Bone remodeling
0302 clinical medicine
Medicine
Spectroscopy
Cells
Cultured
Bone mineral
Aged
80 and over
Osteoblast
General Medicine
femoral head
Middle Aged
3. Good health
Computer Science Applications
medicine.anatomical_structure
Female
Adult
medicine.medical_specialty
BMP2
030209 endocrinology & metabolism
Bone morphogenetic protein
Bone morphogenetic protein 2
Catalysis
Bone resorption
Article
Inorganic Chemistry
03 medical and health sciences
BMD
Internal medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Bone Morphogenetic Protein Receptors
Type I
Aged
Osteoblasts
business.industry
Organic Chemistry
CK2.3
medicine.disease
Alkaline Phosphatase
osteoporosis
Peptide Fragments
osteoarthritis
030104 developmental biology
Endocrinology
Linear Models
business
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 23
ISSN: 1422-0067
DOI: 10.3390/ijms20235877
Popis: Bone is one of the most important organs in the human body. It provides structure, function, and protection for other vital organs
therefore, bone maintenance and homeostasis are critical processes. As humans age, their bone mineral density decreases, which leads to diseases like osteoporosis. This disease affects one in two women and one in five men aged 50 and over. As the aging population increases, the interest and significance of studying this debilitating bone disease becomes more relevant. Current therapeutic products for osteoporosis have many side effects and can be taken for a limited number of years. Most therapeutic products only focus on decreasing bone resorption, not increasing bone formation. Bone morphogenetic protein 2 is an essential growth factor that drives osteoblast differentiation and activity and is essential for bone formation. However, usage in the clinic is unsuccessful due to several side effects. Recently, a signaling disparity in bone marrow stromal cells within the bone morphogenetic protein pathway that led to decreased bone morphogenetic protein 2 responsiveness was identified in patients diagnosed with osteoporosis. However, it is unclear how other cell populations, especially osteoblasts, which are key players in bone remodeling, are affected and whether the bone morphogenetic protein pathway is affected during osteoporosis. Our research group designed a novel peptide, casein kinase 2.3, that acts downstream of the bone morphogenetic receptor type Ia and increases bone mineralization in murine cells and primary bovine osteoblasts. The aim of the study presented here was to compare the responsiveness of osteoblasts to bone morphogenetic protein 2 and casein kinase 2.3, especially in patients diagnosed with osteoporosis. Mature osteoblasts were extracted from patients diagnosed with osteoporosis or osteoarthritis from Christiana Care Hospital in Newark, Delaware. They were stimulated with either bone morphogenetic protein 2 or casein kinase 2.3, and their effect on osteoblast activity was determined. The osteoporotic patients showed no mineralization response to bone morphogenetic protein 2 stimulation, while the osteoarthritis patients significantly responded to bone morphogenetic protein 2 stimulation. Furthermore, markers for osteoblast activity were increased by casein kinase 2.3, which was in sharp contrast to bone morphogenetic protein 2. This further supports a major bone morphogenetic protein signaling disparity in both the elderly and those suffering with osteoporosis. Both patient types did significantly respond to casein kinase 2.3. Further analysis of the bone morphogenetic protein pathway could lead to new therapeutic products for osteoporosis.
Databáze: OpenAIRE
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