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Critical Reviews™ in Immunology
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ISSN 印刷: 1040-8401
ISSN オンライン: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i5.20
pages 423-433

Insights into Monocyte-Driven Osteoclastogenesis and Its Link with Hematopoiesis: Regulatory Roles of PECAM-1 (CD31) and SHP-1

Yue Wu
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
Joseph Madri
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA

要約

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.


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