Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with α9β1 and α4β1 integrins

被引：162

作者：

Grassinger, Jochen ^{[1
]}

Haylock, David N. ^{[1
]}

Storan, Melonie J. ^{[1
]}

Haines, Gemma O. ^{[1
]}

Williams, Brenda ^{[1
]}

Whitty, Genevieve A. ^{[1
]}

Vinson, Andrew R. ^{[1
]}

Be, Cheang Ly ^{[1
]}

Li, Songhui ^{[1
]}

Sorensen, Esben S. ^{[2
]}

Tam, Patrick P. L. ^{[3
]}

Denhardt, David T. ^{[4
,5
]}

Sheppard, Dean

Choong, Peter F. ^{[6
,7
]}

Nilsson, Susan K. ^{[1
,8
]}

机构：

[1] Australian Stem Cell Ctr, Clayton, Vic, Australia

[2] Univ Aarhus, Dept Mol Biol, DK-8000 Aarhus C, Denmark

[3] Univ Sydney, Embryol Unit, Childrens Med Res Inst, Westmead, NSW 2145, Australia

[4] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA

[5] Canc Inst New Jersey, Trenton, NJ USA

[6] St Vincents Hosp Melbourne, Dept Orthopaed, Fitzroy, Vic, Australia

[7] Univ Melbourne, St Vincents Hosp Melbourne, Dept Surg, Fitzroy, Vic 3065, Australia

[8] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

来源：

BLOOD | 2009年 / 114卷 / 01期

基金：

英国医学研究理事会;

关键词：

COLONY-STIMULATING FACTOR; RAT-KIDNEY CELLS; BONE-MARROW; IN-VITRO; ALPHA-4; INTEGRINS; PHYSIOLOGICAL-PROPERTIES; STRUCTURAL REQUIREMENTS; NONPHOSPHORYLATED FORMS; NEUTROPHIL MIGRATION; ADHESIVE PROPERTIES;

D O I：

10.1182/blood-2009-01-197988

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 alpha(9)beta(1) integrin. The N-terminal thrombin cleavage fragment of OPN through its binding to the alpha(9)beta(1) and alpha(4)beta(1) integrins plays a key role in the attraction, retention, regulation, and release of hemopoietic stem and progenitor cells to, in, and from their BM niche. Thrombin-cleaved OPN (trOPN) acts as a chemoattractant for stem and progenitor cells, mediating their migration in a manner that involves interaction with alpha(9)beta(1) and alpha(4)beta(1) integrins. In addition, in the absence of OPN, there is an increased number of white blood cells and, specifically, stem and progenitor cells in the peripheral circulation. (Blood. 2009; 114:49-59)

引用

页码：49 / 59

页数：11

共 60 条

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Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin) [J].