Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with α9β1and α4β1 integrins

Abstract

Osteopontin (OPN), a multifunctional acidic glycoprotein, expressed by osteoblasts within the endosteal region of the bone marrow (BM) suppresses the proliferation of hemopoietic stem and progenitor cells and also regulates their lodgment within the BM after transplantation. Herein we demonstrate that OPN cleavage fragments are the most abundant forms of this protein within the BM. Studies aimed to determine how hemopoietic stem cells (HSCs) interact with OPN revealed for the first time that murine and human HSCs express α9β1 integrin. The N-terminal thrombin cleavage fragment of OPN through its binding to the α9β 1 and α4β1 integrins plays a key role in the attraction, retention, regulation..