Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells

Hideaki Nakajima; Miyuki Ito; Yoshihiro Morikawa; Tadasuke Komori; Yumi Fukuchi; Fumi Shibata; Shinichiro Okamoto; Toshio Kitamura

doi:10.1016/j.bbrc.2009.09.067

Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells

Hideaki Nakajima
, Miyuki Ito
, Yoshihiro Morikawa
, Tadasuke Komori
, Yumi Fukuchi
, Fumi Shibata
, Shinichiro Okamoto
, Toshio Kitamura

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	65-70
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	390
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2009.09.067
Publication status	Published - 2009 Dec 4
Externally published	Yes

Keywords

Hematopoietic stem cells
Osteoblast
SFRP
Secreted frizzled-related protein
Self-renewal
Wnt

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2009.09.067

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title = "Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells",

abstract = "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.",

keywords = "Hematopoietic stem cells, Osteoblast, SFRP, Secreted frizzled-related protein, Self-renewal, Wnt",

author = "Hideaki Nakajima and Miyuki Ito and Yoshihiro Morikawa and Tadasuke Komori and Yumi Fukuchi and Fumi Shibata and Shinichiro Okamoto and Toshio Kitamura",

note = "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. ",

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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.

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KW - Osteoblast

KW - SFRP

KW - Secreted frizzled-related protein

KW - Self-renewal

KW - Wnt

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Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells

Abstract

Keywords

ASJC Scopus subject areas

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