THE EFFECT OF BONE MORPHOGENETIC PROTEIN-2 AND CASEIN KINASE 2.3 ON OSTEOCLAST ACTIVITY WITHIN OSTEOPOROTIC AND OSTEOARTHRITIC PATIENTS
| Author(s) | MacMurray, Connor | |
| Date Accessioned | 2024-09-20T15:13:29Z | |
| Date Available | 2024-09-20T15:13:29Z | |
| Publication Date | 2023-05 | |
| Abstract | Osteoporosis (OP) is a debilitating disease characterized by low bone mineral density (BMD) resulting from an imbalance between two types of bone cells: osteoclasts and osteoblasts. Osteoblasts synthesize bone while osteoclasts resorb bone. Although OP affects one in four women and one in five men over the age of fifty, there are few treatments and no cure. One anabolic treatment that has been approved by the Food and Drug Administration (FDA) is recombinant human Bone Morphogenetic Protein-2 (rhBMP-2). BMP-2 is a growth factor which activates canonical and non-canonical Smad signaling and leads to increased bone mineralization. However, there are various side-effects with this drug and it has been established that primary osteoblasts isolated from OP patients are unresponsive to BMP-2 stimulation. A novel peptide, Casein Kinase 2.3 (CK2.3), was developed to utilize the BMP-2 signaling pathway without exogenous BMP-2. This peptide increases bone mineralization and decreases osteoclast activity in mouse models and cell lines. However, in humans, its effects on osteoclasts are unknown. To further explore this, bone marrow cells were isolated from femoral heads of patients that underwent hip replacement surgery. The cells were differentiated with Macrophage Colony Stimulating Factor (M-CSF) and Receptor Activator of Nuclear Kappa-B Ligand (RANKL). The presence of osteoclasts was confirmed using a Tartrate Resistant Acid Phosphatase (TRAP) staining kit along with a hematoxylin stain. This experiment was conducted first in order to construct a functional model of isolating viable osteoclasts from human patients. Following this experiment, BMP-2 and CK2.3 were added to experimental groups following M-CSF stimulation. BMP-2 was shown to increase osteoclastogenesis within osteoarthritic and osteoporotic patients while CK2.3 decreased osteogenesis. These findings support the notion that CK2.3 could be used as a potential therapeutic for osteoporosis as it effectively reduces osteoclastogenesis. | |
| Advisor | enter | |
| Program | enter | |
| URL | https://udspace.udel.edu/handle/19716/35007 | |
| Language | en_US | |
| Publisher | University of Delaware | |
| Title | THE EFFECT OF BONE MORPHOGENETIC PROTEIN-2 AND CASEIN KINASE 2.3 ON OSTEOCLAST ACTIVITY WITHIN OSTEOPOROTIC AND OSTEOARTHRITIC PATIENTS | |
| Type | Thesis |