Disease relevance of Sfrp1

• Ablation of sFRP-1 also increased osteoclastogenesis in vitro, although changes in bone resorption were not observed in intact animals in vivo [1].

High impact information on Sfrp1

• Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region [2].
• By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant [2].
• Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus [3].
• Recombinant sFRP-1 dose-dependently inhibited osteoclast formation in osteoblast/spleen co-cultures, RANKL + M-CSF-treated splenic cultures, and RANKL-treated RAW264.7 cell cultures, indicating a direct action of sFRP-1 on hematopoietic cells [4].
• Our findings demonstrate that deletion of sFRP-1 preferentially activates Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults [1].

Biological context of Sfrp1

• Nevertheless, sFRP genes must play quite distinct roles in the morphogenesis of several organ systems [5].
• Despite its broad tissue distribution, ablation of sFRP-1 did not affect blood and urine chemistries, most nonskeletal organs, or cortical bone [1].
• However, sFRP-1-/- mice exhibited increased trabecular bone mineral density, volume, and mineral apposition rate when compared with +/+ controls [1].
• In addition, deletion of sFRP-1 inhibited osteoblast lineage cell apoptosis while enhancing the proliferation and differentiation of these cells in vitro [1].
• FrzA/sFRP-1, a secreted antagonist of the Wnt-Frizzled pathway, controls vascular cell proliferation in vitro and in vivo [6].

Anatomical context of Sfrp1

• Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis [2].
• By complementing these results with in situ hybridization, we revealed new expression domains for Wnt2b and Sfrp1, respectively, in the future primitive streak at the posterior side and in the anterior visceral endoderm before the initiation of gastrulation [7].
• While sFRP1 is specifically expressed in the embryonic metanephros, eye, brain, teeth, salivary gland and small intestine, there is only weak expression of sFRP4 except for the developing teeth, eye and salivary gland [5].
• This study describes a new mechanism whereby osteoblasts regulate osteoclastogenesis through the expression and release of sFRP-1 [4].
• We identified secreted Frizzled-related protein-1 (sFRP-1), which is known to bind to Wnt and inhibit the Wnt signaling pathway, as an osteoblast-derived factor that impinges on osteoclast formation and activity [4].

Regulatory relationships of Sfrp1

• In this study, we report that sFRP-1 is expressed in the heart and in the visceral yolk sac during mouse development, and that sFRP-1 and mWnt-8 display overlapping expression patterns during heart morphogenesis [8].

Other interactions of Sfrp1

• Developmental expression patterns of mouse sFRP genes encoding members of the secreted frizzled related protein family [5].
• Moreover, the anterior visceral endoderm expresses three secreted Wnt antagonists (Sfrp1, Sfrp5, and Dkk1) in partially overlapping domains [7].
• We show here that several Wnt, Frizzled, and secreted frizzled-related protein (sFRP) encoding mRNAs are present during mouse pancreatic morphogenesis [9].

Analytical, diagnostic and therapeutic context of Sfrp1

• Involvement of FrzA/sFRP-1 and the Wnt/frizzled pathway in ischemic preconditioning [10].

References