TY - JOUR
T1 - Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells
AU - Nakajima, Hideaki
AU - Ito, Miyuki
AU - Morikawa, Yoshihiro
AU - Komori, Tadasuke
AU - Fukuchi, Yumi
AU - Shibata, Fumi
AU - Okamoto, Shinichiro
AU - Kitamura, Toshio
N1 - Funding Information:
We thank N. Watanabe, T. Shibata, and S. Saito (FACS Core Laboratory, IMSUT) for FACS sorting. This work was supported in part by a grant from the Ministry of Education, Science, and Culture of Japan.
PY - 2009/12/4
Y1 - 2009/12/4
N2 - Wnt signaling has been implicated in the self-renewal of hematopoietic stem cells (HSCs). Secreted frizzled-related proteins (SFRPs) are a family of soluble proteins containing a region homologous to a receptor for Wnt, Frizzled, and are thought to act as endogenous modulators for Wnt signaling. This study examined the role of SFRPs in HSC regulation. Among the four family members, SFRP-1 and SFRP-2 are specifically induced in the bone marrow in response to myelosuppression, and immunostaining revealed that both proteins were expressed in osteoblasts. Interestingly, SFRP-1 reduced the number of multipotent progenitors in in vitro culture of CD34-KSL cells, while SFRP-2 did not. Furthermore, SFRP-1 compromised the long-term repopulating activity of HSCs, whereas SFRP-2 did not affect or even enhanced it in the same setting. These results indicate that although both SFRP-1 and SFRP-2 act as inhibitors for Wnt signaling in vitro, they differentially affect the homeostasis of HSCs.
AB - Wnt signaling has been implicated in the self-renewal of hematopoietic stem cells (HSCs). Secreted frizzled-related proteins (SFRPs) are a family of soluble proteins containing a region homologous to a receptor for Wnt, Frizzled, and are thought to act as endogenous modulators for Wnt signaling. This study examined the role of SFRPs in HSC regulation. Among the four family members, SFRP-1 and SFRP-2 are specifically induced in the bone marrow in response to myelosuppression, and immunostaining revealed that both proteins were expressed in osteoblasts. Interestingly, SFRP-1 reduced the number of multipotent progenitors in in vitro culture of CD34-KSL cells, while SFRP-2 did not. Furthermore, SFRP-1 compromised the long-term repopulating activity of HSCs, whereas SFRP-2 did not affect or even enhanced it in the same setting. These results indicate that although both SFRP-1 and SFRP-2 act as inhibitors for Wnt signaling in vitro, they differentially affect the homeostasis of HSCs.
KW - Hematopoietic stem cells
KW - Osteoblast
KW - SFRP
KW - Secreted frizzled-related protein
KW - Self-renewal
KW - Wnt
UR - http://www.scopus.com/inward/record.url?scp=70349969528&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349969528&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.09.067
DO - 10.1016/j.bbrc.2009.09.067
M3 - Article
C2 - 19778523
AN - SCOPUS:70349969528
SN - 0006-291X
VL - 390
SP - 65
EP - 70
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -