Recruitment of Osteoclasts from Bone Microvasculature

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): Circulating hematopoietic cells are one potential source of osteoclast (OC) precursors from which bone-resorbing OC develop. These OC precursors are believed to be recruited to sites of bone resorption by a mechanism similar to the current paradigm for the recruitment of leukocytes to sites of inflammation. The hypothesis of this application is that the bone vascular endothelium selectively recruits OC precursors by displaying high levels of the chemokine stromal-derived factor-1 (SDF-1) and cellular adhesion molecules in its surface, which first slow, then arrest OC precursors, allowing for their activation, transendothelial migration, and subsequent development into bone-resorbing OC in response to these and other signals within an area of active remodeling. Under inflammatory conditions, an increase in adhesion molecule expression by both vascular endothelial cells and OC precursors may increase the recruitment of OC precursors, thus contributing to the increase in bone resorption observed during inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and periodontal disease. However, the presence of anti-inflammatory molecules such as estrogen and transforming growth factor (TGF)-beta may dampen the effects of inflammation on OC precursor recruitment and development.