Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation.
Differentiation of hematopoietic stem cells (HSCs) after birth is largely restricted to the bone marrow cavity, where HSCs are associated closely with osteoblasts (OBs). How OBs localize HSCs to the endosteal niche remains unclear. To explore adhesive interactions between HSCs and OBs, a cell blot analysis was used that revealed 2 major bands that corresponded to monomers and multimers of annexin II (Anxa2). Immunohistochemistry revealed that OBs and marrow endothelial cells express Anxa2 at high levels. Function-blocking studies confirmed that Anxa2 mediates HSC adhesion mainly via the N-terminal portion of the Anxa2 peptide. Adhesion of HSCs to OBs derived from Anxa2-deficient animals (Anxa2(-/-)) was significantly impaired compared with OBs obtained from wild-type animals (Anxa2(+/+)). Moreover, fewer HSCs were found in the marrow of Anxa2(-/-) versus Anxa2(+/+) animals. Short-term lodging, engraftment, and survival of irradiated mice with whole marrow cells were substantially inhibited by N-terminal peptide fragments of Anxa2 or anti-Anxa2 antibodies. Similar findings were noted in long-term competitive repopulation studies. Collectively, these findings reveal that Anxa2 regulates HSC homing and binding to the bone marrow microenvironment and suggest that Anxa2 is crucial for determining the bone marrow niche of HSCs.
Jung
Younghun
Y
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Wang
Jingcheng
J
Song
Junhui
J
Shiozawa
Yusuke
Y
Wang
Jianhua
J
Havens
Aaron
A
Wang
Zhuo
Z
Sun
Yan-Xi
YX
Emerson
Stephen G
SG
Krebsbach
Paul H
PH
Taichman
Russell S
RS
D000818:Animals; D017306:Annexin A2 / Q000502:physiology*; D001853:Bone Marrow; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000737:chemistry*; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000737:chemistry*
D017306:Annexin A2