Stanniocalcin 1 Alters Muscle and Bone Structure and Function in Transgenic Mice

Filvaroff, Ellen; Guillet, Susan; Zlot, Constance; Bao, Min; Ingle, Gladys S.; Steinmetz, Hope; Hoeffel, J. M.; Bunting, Stuart; Ross, P. James; Carano, Richard A.D.; Powell-Braxton, Lyn; Wagner, Graham F.; Eckert, Renee; Gerritsen, Mary E.; French, Dorothy

doi:10.1210/en.2001-211424

Cited by 100 publications

(85 citation statements)

References 44 publications

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“…Overexpression and knockdown study of STC1 led to the acceleration and retardation of osteogenic development respectively (Yoshiko et al 2003). STC1 is also expressed in chondrocytes and may also stimulate chondrocyte proliferation in cartilage matrix (Jiang et al 2000, Filvaroff et al 2002. In transgenic mice expressing human STC2, growth restriction and developmental retardation were observed in both prenatal and postnatal stages, and ossification was reduced in different endochondral skeletal elements (Gagliardi et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Ichikawa

Horie‐Inoue²,

Ikeda³

et al. 2007

Journal of Molecular Endocrinology

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Vitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent g-glutamyl carboxylase (GGCX), we have previously shown that vitamin K 2 is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K 2 isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K 2 isoform MK-7, vitamin K 1 , or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K 2 modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Ichikawa

Horie‐Inoue²,

Ikeda³

et al. 2007

Journal of Molecular Endocrinology

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“…Transgenic mice overexpressing STC1 exhibit a significant reduction in birth weight and reduced body size in the adult [35,36], suggesting that STC1 has a regulatory role in mammalian fetal or postnatal growth. On the other hand, STC1-deficient mice show a normal phenotype and are fertile, indicating that STC1 may not be essential for growth or reproduction [37] or that STC2 may have compensated for the effect of STC1 [38].…”

Section: Expression Of Stanniocalcin-1 In the Equine Endometriummentioning

confidence: 99%

Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period

et al. 2011

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Abstract.A factor responsible for progression to pregnancy establishment in the mare has not been definitively characterized. To identify factors possibly involved in the establishment of equine pregnancy, the endometrium was collected from day 13 (day 0=day of ovulation) cyclic and day 13, 19 and 25 pregnant animals. From initial subtractive hybridization studies, a calcium regulating factor, Stanniocalcin-1 (STC1) mRNA, was found as a candidate molecule expressed uniquely in the pregnant endometrium. Endometrial expression of STC1 mRNA was noted on day 19 and was markedly increased in the day 25 gravid endometrium. STC1 protein was found in the extracts of day 25 gravid endometrium and immunochemically localized in the uterine glands. In addition, STC1 protein was detected in uterine flushing media collected from day 25 pregnant mares. High concentrations of estradiol-17β (E2) were detected in day 25 conceptuses. E2 levels were much higher in the gravid endometrium than in other regions, whereas progesterone levels did not differ among the samples from different endometrial regions. Expression of STC1 mRNA, however, was not significantly upregulated in cultured endometrial explants treated with various concentrations of E2 (0.01-100 ng/ml) with or without 10 ng/ml progesterone. These results indicate that an increase in STC1 expression appears to coincide with capsule disappearance in the conceptus, and suggest that STC1 from the uterine glands likely plays a role in conceptus development during the pregnancy establishment period in the mare. Key words: Endometrium, Equine, Estradiol-17β, Stanniocalcin-1 (STC1), Uterine secretion (J. Reprod. Dev. 57: [203][204][205][206][207][208][209][210][211] 2011) he establishment of equine pregnancy is a unique and long process, during which a series of physical and possibly biochemical interactions are required between the conceptus and uterus. The equine conceptus first enters into the uterus on days 6-8 of pregnancy (day 0=day of ovulation) [1] and then begins to transmigrate throughout the entire uterine body and horns until approximately day 16 of pregnancy [2][3][4]. The frequency at which a conceptus moves from one uterine horn to another increases up to 10-20 times per day [5]. The conceptus ceases migration and lodges at the caudal portion of one of the uterine horns, known as "fixation", on approximately days 16-18 of pregnancy [2]. Between days 11 and 16 of pregnancy, the conceptus rapidly expands its volume, but keeps its spherical shape surrounded by a unique, smooth structure called a "capsule" [6,7] that emerges beneath the zona pellucida on days 6-8 of pregnancy. The capsule is an acellular mucin-like glycoprotein [8] that is structurally strong and is considered essential for the survival of the conceptus and continuation of pregnancy [9,10]. Together with peristaltic myometrial contractions, the capsule is likely to give motility to the conceptus, although the precise stimulus for conceptus migration is unknown. Thereafter, the capsule disappears by d...

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“…A number of studies, mostly correlative, of mammalian STC1 mRNA and protein expression have ascribed roles to STC1 ranging from angiogenesis (Kahn et al, 2000;Bell et al, 2001), bone and muscle development (Jiang et al, 2000;Filvaroff et al, 2002;Varghese et al, 2002;Yoshiko et al, 2003), inflammation (Iyer et al, 1999;Kanellis et al, 2003), cellular metabolism (McCudden et al, 2002;Ellard et al, 2007) and cancer (Fujiwara et al, 2000;Ismail et al, 2000;Okabe et al, 2001;Welcsh et al, 2002). Establishing the functional importance and relevance of these putative functions has proved difficult; moreover, STC1-null mice housed in standard laboratory conditions have no obvious phenotype (Chang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress

2009

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Mammalian Stanniocalcin-1 (STC1) is a glycoprotein that has been implicated in various biological processes including angiogenesis. Aberrant STC1 expression has been reported in breast, ovarian and prostate cancers, but the significance of this is not well understood. Here, we report that oxidative stress caused a 40-fold increase in STC1 levels in mouse embryo fibroblasts (MEFs). STC1À/À MEFs were resistant to growth inhibition and cell death induced by H 2 O 2 or by 20% O 2 (which is hyperoxic for most mammalian cells); this is the first phenotype reported for STC1-null cells. STC1À/À cells had higher levels of activated MEK and ERK1/2 than their wild-type (WT) counterparts, and these levels were all reduced by stable expression of exogenous STC1 in STC1À/À cells. Furthermore, pharmacological inhibition by PD98059 or UO126 of MEK and therefore of ERK1/2 activation restored sensitivity of STC1À/À cells to oxidative stress. We also found that H 2 O 2 -induced STC1 expression in WT cells was abolished by inhibition of ERK1/2 activation. Thus, the ERK1/2 signaling pathway upregulates STC1 expression, which in turn downregulates the level of activated MEK and consequently ERK1/2 in a novel negative feedback loop. Therefore, STC1 expression downregulates prosurvival ERK1/2 signaling and reduces survival under conditions of oxidative stress.

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Stanniocalcin 1 Alters Muscle and Bone Structure and Function in Transgenic Mice

Cited by 100 publications

References 44 publications

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period

Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress

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