Secreted Frizzled-Related Protein-1 Inhibits RANKL-Dependent Osteoclast Formation

Hausler, K D; Horwood, Nicole J.; Chuman, Yoshiro; Fisher, Jane; Ellis, Jennifer L.; Martın, Thomas; Rubin, Jeffrey S.; Gillespie, Matthew T.

doi:10.1359/jbmr.040807

Cited by 133 publications

(119 citation statements)

References 53 publications

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“…Day 3 and day 10 are the times the major and minor bursts of osteoclastogenesis respectively occur [3,4]. This led us to speculate that SFRP-1 may inhibit osteoclastogenesis, as seen in mice [11,15]. This was confirmed by our in vitro osteoclastogenesis studies, showing that SFRP-1 inhibited osteoclastogenesis in vitro (Fig.…”

Section: Discussionsupporting

confidence: 52%

“…SFRP-1 is a secreted membrane protein that binds directly to Wnt proteins, thereby inhibiting the Wnt signaling pathway [14]. Because of its ability to inhibit osteoclast formation in vitro, it was identified as an osteoclastogenesis inhibitor that was expressed by osteoblasts and chondrocytes in murine bone and cartilage [11]. Its inhibitory role in osteoclastogenesis also was demonstrated in studies in which bone marrow cells isolated from SFRP-1 knockout mice differentiated into osteoclasts 3-to 50-fold more than such cells from wild-type mice [15].…”

Section: Discussionmentioning

confidence: 99%

“…1A) was chosen for further study because of the report that SFRP-1 was an inhibitor of osteoclastogenesis in mice [11]. To confirm the expression of the SFRP-1 gene in the rat follicle cells, RT-PCR was conducted using primers based on the partial gene sequence (Genbank accession no.…”

Section: Gene Expression Profiling In Dental Follicle Cellsmentioning

confidence: 99%

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A DNA microarray analysis of chemokine and receptor genes in the rat dental follicle—Role of secreted frizzled-related protein-1 in osteoclastogenesis

Liu

Wise

2007

Bone

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The dental follicle, a loose connective tissue sac that surrounds the unerupted tooth, appears to regulate the osteoclastogenesis needed for eruption; i.e., bone resorption to form an eruption pathway. Thus, DNA microarray studies were conducted to determine which chemokines and their receptors were expressed chronologically in the dental follicle, chemokines that might attract osteoclast precursors. In the rat first mandibular molar, a major burst of osteoclastogenesis occurs at day 3 with a minor burst at day 10. The results of the microarray confirmed our previous studies showing the gene expression of molecules such as CSF-1 and MCP-1 in the dental follicle cells. Other new genes also were detected, including secreted frizzled-related protein-1 (SFRP-1), which was found to be down-regulated at days 3 and 9. Using rat bone marrow cultures to conduct in vitro osteoclastogenic assays, it was demonstrated that SFRP-1 inhibited osteoclast formation in a concentration-dependent fashion. However, with increasing concentrations of SFRP-1, the number of TRAP-positive mononuclear cells increased suggesting that SFRP-1 inhibits osteoclast formation by inhibiting the fusion of mononuclear cells (osteoclast precursors). Co-culturing bone marrow mononuclear cells and dental follicle cells demonstrated that the dental follicle cells were secreting a product(s) that inhibited osteoclastogenesis, as measured by counting of TRAP-positive osteoclasts. Adding an antibody either to SFRP-1 or OPG partially restored osteoclastogenesis. Adding both anti-SFRP-1 and anti-OPG fully negated the inhibitory effect of the follicle cells upon osteoclastogenesis. These results strongly suggest that SFRP-1 and OPG, both secreted by the dental follicle cells, use different pathways to exert their inhibitory effect on osteoclastogenesis. Based on these in vitro studies of osteoclastogenesis, it is likely that the down-regulation of SFRP-1 gene expression in the dental follicle at days 3 and 9 is a contributory factor in allowing the major and minor bursts of osteoclastogenesis to occur. Thus, inhibition of SFRP-1 gene expression in combination with inhibition of OPG gene expression likely are critical events in enabling alveolar bone resorption to occur such that teeth will erupt.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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A DNA microarray analysis of chemokine and receptor genes in the rat dental follicle—Role of secreted frizzled-related protein-1 in osteoclastogenesis

Liu

Wise

2007

Bone

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“…sFRP-1 gene expression is also up-regulated by PGE 2 and IL-11 treatment of murine stromal cells and OBs; however, incubation of these cells with Dex, vitamin D 3 , PTH, and IL-1, -4, -10, and -18 had no effect on mRNA levels of the Wnt antagonist [Hausler et al, 2004]. Thus, mechanisms controlling sFRP-1 expression appear to vary among species.…”

Section: Discussionmentioning

confidence: 93%

“…This may be caused by increased osteoblastogenesis [Manolagas, 2000], which also occurs in the sFRP-1 knockout mice [Bodine et al, 2004]. However, another potential mechanism is the ability of sFRP-1 to bind and antagonize receptor activator of NF-kb ligand Hausler et al, 2004], which is an important stimulator of osteoclastogenesis [Manolagas, 2000].…”

Section: Discussionmentioning

confidence: 99%

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Bodine¹,

Billiard²,

Moran³

et al. 2005

J of Cellular Biochemistry

157

113

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Mechanisms controlling human bone formation remain to be fully elucidated. We have used differential display-polymerase chain reaction analysis to characterize osteogenic pathways in conditionally immortalized human osteoblasts (HOBs) representing distinct stages of differentiation. We identified 82 differentially expressed messages and found that the Wnt antagonist secreted frizzled-related protein (sFRP)-1 was the most highly regulated of these. Transient transfection of HOBs with sFRP-1 suppressed canonical Wnt signaling by 70% confirming its antagonistic function in these cells. Basal sFRP-1 mRNA levels increased 24-fold during HOB differentiation from pre-osteoblasts to pre-osteocytes, and then declined in mature osteocytes. This expression pattern correlated with levels of cellular viability such that the preosteocytes, which had the highest levels of sFRP-1 mRNA, also had the highest rate of cell death. Basal sFRP-1 mRNA levels also increased 29-fold when primary human mesenchymal stem cells were differentiated to osteoblasts supporting the developmental regulation of the gene. Expression of sFRP-1 mRNA was induced 38-fold following prostaglandin E 2 (PGE 2 ) treatment of pre-osteoblasts and mature osteoblasts that had low basal message levels. In contrast, sFRP-1 expression was down-regulated by as much as 80% following transforming growth factor (TGF)-b1 treatment of preosteocytes that had high basal mRNA levels. Consistent with this, treatment of pre-osteoblasts and mature osteoblasts with PGE 2 increased apoptosis threefold, while treatment of pre-osteocytes with TGF-b1 decreased cell death by 50%. Likewise, over-expression of sFRP-1 in HOBs accelerated the rate of cell death threefold. These results establish sFRP-1 as an important negative regulator of human osteoblast and osteocyte survival.

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Secreted Wnt Inhibitors or Modulators

Bovolenta

Gorny

Esteve

et al. 2014

WNT Signaling in Development and Disease

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Secreted Frizzled-Related Protein-1 Inhibits RANKL-Dependent Osteoclast Formation

Cited by 133 publications

References 53 publications

A DNA microarray analysis of chemokine and receptor genes in the rat dental follicle—Role of secreted frizzled-related protein-1 in osteoclastogenesis

A DNA microarray analysis of chemokine and receptor genes in the rat dental follicle—Role of secreted frizzled-related protein-1 in osteoclastogenesis

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Secreted Wnt Inhibitors or Modulators

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