RT Journal Article ID 3c2e6e1e2ed04a04 A1 Wu, Yue A1 Madri, Joseph T1 Insights into Monocyte-Driven Osteoclastogenesis and Its Link with Hematopoiesis: Regulatory Roles of PECAM-1 (CD31) and SHP-1 JF Critical Reviews™ in Immunology JO CRI YR 2010 FD 2010-11-04 VO 30 IS 5 SP 423 OP 433 K1 megakaryocyte K1 osteoclast K1 hematopoiesis K1 PECAM-1 K1 SHP-1 K1 monocyte AB Osteoclasts are derived from hematopoietic cells of monocyte-macrophage lineage. Osteoclastogenesis is orchestrated by the migration of monocytic osteoclast progenitor cells in close proximity to bone surfaces destined for resorption. Although the overall roles of monocyte migratory behavior in osteoclastogenesis remain enigmatic, impaired monocyte migration can lead to either decreased or increased osteoclastogenesis, which appears contingent upon the roles of migration in either fusion events required for osteoclast formation or terminal differentiation of osteoclasts. The cell adhesion molecule PECAM-1 (platelet endothelial cell adhesion molecule 1), in concert with the tyrosine phosphatase SHP-1 (Src homology 2-containing protein tyrosine phosphatase 1) and tyrosine kinase Syk-1 (spleen tyrosine kinase 1), functions as a negative regulator of osteoclastogenesis. Both PECAM-1 (CD31) and SHP-1 knockout mice exhibit not only increased osteoclastogenesis but also abnormal hematopoiesis, which is suggestive of the intricate interplay between hematopoiesis and osteoclastogenesis. Interestingly, the most pronounced effect of PECAM-1 deficiency on hematopoiesis is reflected by excessive megakaryocytopoiesis. Emerging data have suggested the role of megakaryocytes in bone remodeling. Megakaryocytopoiesis-osteoclastogenesis interactions are discussed herein, reconciling the discrepancies shown by different studies in this area. PECAM-1 and non-receptor tyrosine phosphatase polymorphisms have been revealed in a spectrum of diseases. The complex regulatory roles of PECAM-1 and SHP-1 in vivo suggest the potential utilization of polymorphisms of these genes for diagnostic purposes. PB Begell House LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,76236f9f086f9f9f,3c2e6e1e2ed04a04.html