THE EFFECT OF BONE MORPHOGENETIC PROTEIN-2 AND CASEIN KINASE 2.3 ON OSTEOCLAST ACTIVITY WITHIN OSTEOPOROTIC AND OSTEOARTHRITIC PATIENTS
Date
2023-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
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.