Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

Legacy Department


Committee Chair/Advisor

Vyavahare, Narendra R

Committee Member

Simionescu , Dan T

Committee Member

LaBerge , Martine

Committee Member

Bateman , Ted


Vascular calcification occurs during physiological aging and is clinically recognized as a major risk factor for myocardial infarction, systolic hypertension, heart failure and coronary insufficiency caused by loss of aortic recoil. Medial arterial calcification is an active remodeling process that involves the deposition of bone-specific matrix in close association with elastic fibers. Elastin, a major structural protein in the extracellular matrix of arterial walls, provides elastic recoil to the arteries. Increasing evidence suggests that vascular calcification share features with skeletal bone formation such as bone matrix deposition and bone resorption. Bone morphogenetic proteins and bone cells have been found in explanted atherosclerotic plaques. In bone, a homeostasis is maintained by its two major cell types; osteoblasts and osteoclasts. Osteoblasts form new bone matrix and osteoclasts, multinucleated giant cells which are derived from bone marrow progenitor cells, are responsible for bone resorption.
Osteoclasts are derived from the monocyte/macrophage lineage of bone marrow progenitor cells. Bone marrow progenitor cells differentiate into osteoclasts by cytokines released by neighboring cells like activated T-lymphocytes, osteoblasts or bone marrow stromal cells. Receptor activator of nuclear factor-kB ligand (RANKL) and 1α, 25(OH)2D3 (Vitamin D3) are examples of stimulates for osteoclast activation.
The objective of this project was to evaluate the use of osteoclasts differentiated from bone marrow progenitor cells as a cell therapy to treat vascular elastin-specific calcification.



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