Kaiming Wu

EFFECTS OF P2Y12 DEFICIENCIES ON OSTEOCLAST DEFECTS AND IMPLICATIONS FOR OSTEOLYTIC BONE LESIONS. Kaiming Wu¹, Desiree Floyd², and Katherine Weilbaecher².Biology Department, Washington University, St. Louis, MO¹; Department of Molecular Oncology, Washington University Medical School, St. Louis, MO²

P2Y12 is a membrane nucleotide receptor known to be on platelets as part of the fibrinogen receptor activation pathway. It acts in conjunction with other receptors of the P2Y family, most notably P2Y1. We show here that P2Y12 is also located on osteoclasts through both semi-quantitative as well as real-time PCR. We investigated the effects of P2Y12 deficiencies in osteoclastogenesis and found P2Y12 deficiency to correlate with significantly less osteoclast area and less production of the osteoclast marker TRAP (Tartrate resistant acid phosphatase) after stimulation of bone marrow macrophages with MCSF and RANKL. This correlation implies possible protection of P2Y12 deficient individuals from osteolytic bone tumors. P2Y12 -/- and +/+ mice were given intratibial injections of B16 melanoma cells and observed for tumor growth via luciferase imaging. Results of bone histology for experimental mice would clarify the correlation between P2Y12 deficiency and bone tumor growth.