Disease relevance of FRZB

• OBJECTIVE: To confirm the association of 2 variants of the Frizzled-related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes [1].
• The loss of FrzB in gastric cancer suggests that it acts as a tumour suppressor [2].
• Evidence for a differential association of the Arg200Trp single-nucleotide polymorphism in FRZB with hip osteoarthritis and osteoporosis [3].
• Expression of sFRP3 which promoter has no CpG island was downregulated in only a few of colorectal tumor samples (7/105) [4].
• Here, Fritz Bach and colleagues discuss the importance of endothelial cell activation, platelet aggregation and other aspects of thrombosis, as well as the contribution of host natural killer cell and monocyte activation in overcoming this next barrier to prolonged xenograft survival [5].

Psychiatry related information on FRZB

• Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OMIM 167400), is an inherited disease causing intense burning rectal, ocular, and submandibular pain and flushing [6].
• The author concludes that "when seeking to explain the nature and significance of racism in contemporary Europe, we might usefully begin by focussing on the processes involved in the construction and reproduction of the Nation-State...." (SUMMARY IN FRE AND SPA)[7]
• According to the results, a good half of this decrease is attributable to the trends in real wages and alcohol consumption." (SUMMARY IN FRE)[8]
• Rorschach responses of three subjects were used to stimulate the type of role-playing popularized by Fritz Perls' Gestalt therapy [9].
• In addition, we also viewed migration as an action with the potential to modify gender relations and alter future migration decision-making, as women gain experience in the labour market and exposure to new social and cultural environments." (SUMMARY IN FRE AND SPA)[10]

High impact information on FRZB

• Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer [11].
• In this report, we find that FRP and inhibin modulate both the induction of haemoglobin accumulation in a human erythroleukaemic cell line, K562, and the proliferation of erythroid progenitor cells in human bone marrow culture [12].
• In contrast to the effects of GnRH and other reported gonadal gonadotropin releasing fractions, the action of FRP is not mediated by GnRH receptors [13].
• Neither FeCl3 in combinations with H2O2, nor Fe3+ or Fe2+ chelated with EDTA, nor Zn2+-protoporphyrin IX, nor protoporphyrin IX caused significant inactivation of FRP [14].
• We provide evidence suggesting that skeletal myogenesis in the head is induced by the BMP inhibitors, Noggin and Gremlin, and the Wnt inhibitor, Frzb [15].

Chemical compound and disease context of FRZB

• Two common single nucleotide polymorphisms (SNPs) that code for the substitution of conserved arginine residues have previously been identified in FRZB and found to be associated with osteoarthritis (OA) [16].
• Here, we examined the biological effects of Frzb/sFRP3 on an androgen-independent prostate cancer cell model [17].

Biological context of FRZB

• Phosphorylation of SMAD-1/-5 and downregulation of FRZB were confirmed in vivo in a mouse model of joint surface injury [18].
• However, genotyping showed lack of association for a nonsynonymous single-nucleotide polymorphism in tumor necrosis factor alpha-induced protein 6, whereas a single-nucleotide polymorphism in FRZB resulting in an Arg324Gly substitution at the carboxyl terminus was associated with hip OA in the female probands (P = 0.04) [19].
• In addition, a haplotype coding for substitutions of two highly conserved arginine residues (Arg200Trp and Arg324Gly) in FRZB was a strong risk factor for primary hip OA, with an odds ratio of 4.1 (P = 0.004) [19].
• Here, microsatellite targeting of eight candidate genes in this region from 2q23-2q32 demonstrated significant associations with the tumor necrosis factor alpha-induced protein 6 gene in all probands and the integrin alpha 6 and frizzled motif associated with bone development (FRZB) genes in female probands [19].
• CONCLUSION: Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes [1].

Anatomical context of FRZB

• HB-EGF and FRZB were poorly expressed in purified polyclonal plasma cells [20].
• Results from PCR-based experiments suggest that the FRZB/sFRP3 gene is not deleted in OGS cell lines, however, karyotyping shows gross abnormalities involving chromosome 2 (location of the FRZB gene) in five of twelve OGS-derived cell lines [21].
• METHODS: RNA was extracted from the articular cartilage chondrocytes of 25 individuals who had undergone joint replacement for OA and who were heterozygous for one of the two FRZB SNPs [16].
• Crescent is a Frizzled-related protein that inhibits Wnt-8c and is expressed in anterior endoderm during gastrulation [22].
• Here we examined expression of WNT and the WNT inhibitor, secreted frizzled-related protein (FRP), in RA and OA synovium by reverse transcription-PCR [23].

Associations of FRZB with chemical compounds

• The size of the pool of 0.1% Triton soluble beta-catenin tended to decrease in myocardial samples with high sFRP 3 and 4 expression levels [24].
• FRP is highly potent (50% effective concentration (EC50) approximately 25 pM) in stimulating the secretion and biosynthesis of FSH but not of LH or any other pituitary hormone [13].
• A factor from conditioned medium of a leukaemia cell line has been isolated which can induce mouse Friend cells to become benzidine-positive, and which shares a similar N-terminal sequence with porcine FRP [12].
• Therefore, anti-FRP mAbs were thought to induce the fusion via an integrin system(s) [25].
• Here, Irving Fritz and Edoardo Arrigoni-Martelli review the evidence that carnitine and its O-acyl derivatives also influence membrane fluidity, ion channel functions, smooth muscle contractility, membrane stability and cardiac functions [26].

Other interactions of FRZB

• A meta-analysis of these data and those from previously published reports indicated a strong association between the FRZB G324 allele (P < 0.0003) and suggested that an ASPN allele is protective against the risk of knee OA in Caucasians (P < 0.02) [27].
• In contrast, Dkk1 and FrzB were not expressed in normal colon [2].
• FRZB encodes secreted frizzled-related protein 3, which is a soluble antagonist of wingless (wnt) signaling [19].
• Previous studies have shown that three members of the Wnt signaling pathway, the ligand WNT5A, the receptor FZ4, and the Wnt antagonist FRZB1, are implicated in the formation and differentiation of the digits [28].
• The present study shows that levels of SFRPI, SFRP3 and SFRP5 mRNAs are also abnormal in RP, giving rise to idiosyncratic expression patterns [29].

Analytical, diagnostic and therapeutic context of FRZB

• Serum FRP levels were measured by enzyme-linked immunosorbent assay [30].
• The myocardial localization of sFRP 3 and 4 expression was investigated using in situ RT-PCR [24].
• We report here the purification of an FSH releasing protein (FRP) and its characterization by SDS-polyacrylamide gel electrophoresis under non-reducing and reducing conditions and by partial sequence analysis [13].
• In this paper Jeffrey Platt, Fritz Bach and colleagues describe a model of hyperacute rejection and propose that, if hyperacute rejection can be averted for a period after transplantation, prolonged xenograft survival will be possible [31].
• Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2) [32].

References