Hauschka Laboratory - Bone Cell Biology

Vascular Calcification

Pericytes are hypothesized to play a central role in vascular calcification processes, and thus perhaps other types of ectopic bone formation. The normal presence of pericytes in all microvessels, and their mesenchymal stem cell properties that include the capacity to differentiate into osteoblast-like cells, may explain the pathological calcification of atherosclerotic lesions. Pericytes may also be a target for cholesterol-lowering statin drugs that inhibit HMG-CoA reductase-mediated cholesterol biosynthesis. Statins are believed to modulate the cholesterol-rich pre-assembled signaling complexes in cell membranes (caveolae and lipid rafts).

Our research in this area addresses the following problems:

1. What regulates differentiation of pericytes into calcifying cells with an osteogenic, osteoblastic phenotype?
2. Do pre-assembled membrane signaling domains play a critical role in pericyte biology?
3. How does cell-cell contact between macrophage-derived foam cells and the pericyte lineage (mesenchymal stem cells, vascular smmoth muscle cells, osteoblasts?) contribute to the pathophysiology of atherosclerosis and vascular calcification?
    

Application of multi-color flow cytometry has revealed the phenotypic diversity of foam cells and pericytes and will serve as a future foundation for isolation and functional analysis of differentiated sub-populations relevant to atherosclerosis and vascular calcification.

Characterization of the cell-cell interactions and signaling pathways in pericytes that initiate and sustain their osteogenic transdifferentiation could provide the foundation for new therapeutic strategies to treat cardiovascular calcification, atherosclerosis, and possibly other pathology related to ectopic bone formation.