Stanniocalcin 1 (STC1) Protein and mRNA Are Developmentally Regulated During Embryonic Mouse Osteogenesis: the Potential of STC1 as an Autocrine/Paracrine Factor for Osteoblast Development and Bone Formation

Yoshiko, Yuji; Aubin, Jane E.; Maeda, Norihiko

doi:10.1177/002215540205000405

Cited by 34 publications

(25 citation statements)

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“…STC-1 mRNA was found in a wide variety of mammalian tissues having an autocrine or paracrine role modulating phosphate and calcium fluxes between extracellular and intracellular compartments [26]. Similar to our observations were described by Block et al [31] that employed an injury model in which epithelial monolayers were disrupted.…”

Section: Discussionsupporting

confidence: 89%

“…Changes in It was striking to find high and significant up-regulation of stanniocalcin-1 (STC-1) in cells of group C, in comparison to groups A and B (p=0.01). STC-1 mRNA was found in a wide variety of mammalian tissues having an autocrine or paracrine role modulating phosphate and calcium fluxes between extracellular and intracellular compartments [26]. Quantitative measurement of STC-1 by qPCR confirmed the elevated expression in HGF cells after detachment of collagen coat ( Figure 5).…”

Section: Gene Expression Of P2x4 P2x7 Rank-l and Stc-1 In Hgf Cellsmentioning

confidence: 74%

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Strain Reduction of Human Gingival Fibroblasts Induces the ATP Pathway

Weinberg¹

2015

J Interdiscipl Med Dent Sci

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Studies in rats demonstrated that surgical detachment of marginal gingiva from root surfaces induced alveolar bone resorption via activation of ATP receptor P2X4. Our aim was to study the effects of strain release of human gingival fibroblasts by detachment of collagen coat from culture dishes. Changes in cell shape, extracellular ATP, cell calcium and genes relevant to trigger alveolar bone resorption were measured. HGF cells from human marginal gingiva explants were seeded on collagen coated culture dishes. In the test group, the collagen coat was detached from culture dish 4-5 days after seeding. Quantification of extracellular ATP was measured by Bioluminescent Assay Kit and changes of intracellular calcium by FLU-AM fluorescence. Real-time PCR was used to examine expression of purinergic receptor P2X4 and P2X7, RANK-L and STC1. Cell length of HGFs grown on plastic surface and on collagen was similar. Reduction in cell length of 45% was measured after detachment of collagen coat. Extracellular ATP raised 10 folds 1 minute after detachment of collagen coat, then declined and returned to control levels 60 minutes later. Ionomycin increased extracellular ATP, while, pretreatment by EGTA, or BAPTA-AM, 30 minutes prior to Ionomycin, reduced significantly extracellular ATP. Reciprocally, addition of ATP increased influx of calcium into HGFs. At the molecular level elevated expression of STC-1, RANK-L and P2X7 was recorded by RT -PCR in detached HGFs, while expression of P2X4 was unchanged. Expression of STC-1, a modulator of cellular calcium and phosphate, P2X7 a calcium ionic channel purinergic receptor and RANK-L a powerful regulator of osteoclastic activity, all were up-regulated significantly. Conclusion:We propose that drop of strain of HGF cells and change in their shape stimulated release of cellular ATP which is signaling through Pi/Ca modulators the molecular activation of osteoclasts.

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Section: Discussionsupporting

confidence: 89%

Section: Gene Expression Of P2x4 P2x7 Rank-l and Stc-1 In Hgf Cellsmentioning

confidence: 74%

Strain Reduction of Human Gingival Fibroblasts Induces the ATP Pathway

Weinberg¹

2015

J Interdiscipl Med Dent Sci

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“…Stc1 expression has been reported in a variety of tissues during early mouse development, especially the skeletal and muscular tissues (13,24,31). Mice that overexpressed a human STC1 transgene (driven by exogenous metallothionein promoter or myosin light-chain promoter) were dwarfed and had decreased bone length (7,25).…”

Section: Discussionmentioning

confidence: 99%

The Murine Stanniocalcin 1 Gene Is Not Essential for Growth and Development

Chang

Cha

Köentgen

et al. 2005

Molecular and Cellular Biology

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The stanniocalcin 1 (STC1) gene is expressed in a wide variety of tissues, including the kidney, prostate, thyroid, bone, and ovary. STC1 protein is considered to have roles in many physiological processes, including bone development, reproduction, wound healing, angiogenesis, and modulation of inflammatory response. In fish, STC1 is a hormone that is secreted by the corpuscles of Stannius and is involved in calcium and phosphate homeostasis. To determine the role of STC1 in mammals, we generated Stc1-null mice by gene targeting. The number of Stc1 ؊/؊ mice obtained was in accordance with Mendelian ratios, and both males and females produced offspring normally. No anatomical or histological abnormalities were detected in any tissues. Our results demonstrated that Stc1 function is not essential for growth or reproduction in the mouse.Stanniocalcin 1 (STC1) is a glycoprotein that was first identified in fish as a hormone secreted by the corpuscles of Stannius, an organ unique to bony fish. It is secreted into the blood in response to elevated calcium and has potent activity on the gills, kidneys, and gut to regulate calcium absorption and phosphate excretion (8,16,17). We and others have identified two related mammalian genes encoding STC1 and STC2 that are paralogs of the fish gene (2,4,6,11,20,21). Mammalian STCs are expressed in a wide variety of tissues, including the kidney, ovary, prostate, thyroid, and spleen.Given its role in fish, initial functional analyses of mammalian STC1 focused on determining whether its role in regulating blood calcium has been conserved. In vivo studies in which recombinant STC1 protein was injected into rats indicated that STC1 may regulate blood calcium by increasing renal reabsorption of phosphate, and in vitro experiments showed that STC1 could reduce the flux of calcium across the intestines of rats and swine while increasing absorption of phosphate (19,21,27). Interestingly, expression studies showed strong STC1 production in a variety of tissues during murine development and a general down-regulation of expression during postnatal development in all tissues except the ovary, where expression increased. On the basis of these and a variety of other functional and expression studies, it has been proposed that the physiologic roles of STC1 are pleiotropic and include early musculoskeletal development, female reproduction, cell motility, and a cytoprotective role in response to different stressors (13-15, 22, 24, 31-34). Moreover, evidence is also accumulating for a role of STC1 in cancer (reviewed in reference 3).To determine whether STC1 plays a crucial role during normal development and provide a model for examining the function of STC1 in vivo, we generated mice that are null for STC1. We generated two independent lines (L278 and L282) by homologous recombination and examined them for overt abnormalities. MATERIALS AND METHODSTargeting vector construction and generation of Stc1-deficient mice. Genomic DNA encoding STC1 was isolated from a mouse 129 SVJ Lambda FIXII library (...

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“…In addition, STC1 mRNA expression has been found in osteoblasts and articular cartilage of 30-day-old mouse femora (10,18,19). Transgenic mice overexpressing STC1 exhibit significant reduction in birth weight and reduced adult body size, which would suggest a regulatory role for STC1 in mammalian bone growth (20,21).…”

Section: Stanniocalcin (Stc)mentioning

confidence: 99%

Stanniocalcin 1 Acts as a Paracrine Regulator of Growth Plate Chondrogenesis

Yoshiko

Luca

2006

Journal of Biological Chemistry

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During embryogenesis, the expression of mammalian stanniocalcin (STC1) in the appendicular skeleton suggests its involvement in the regulation of longitudinal bone growth. Such a role is further supported by the presence of dwarfism in mice overexpressing STC1. Yet, the STC 1 inhibitory effect on growth may be related to both postnatal metabolic abnormalities and prenatal defective bone formation. In our study, we used an organ culture system to evaluate the effects of STC on growth plate chondrogenesis, which is the primary determinant of longitudinal bone growth. Fetal rat metatarsal bones were cultured in the presence of recombinant human STC (rhSTC). After 3 days, rhSTC suppressed metatarsal growth, growth plate chondrocyte proliferation and hypertrophy/differentiation, and extracellular matrix synthesis. In addition, rhSTC increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, rhSTC increased phosphate uptake, reduced chondrocyte proliferation and matrix synthesis, and induced apoptosis. All these effects were reversed by culturing chondrocytes with rhSTC and phosphonoformic acid, an inhibitor of phosphate transport. The rhSTC-mediated inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was abolished by culturing metatarsals with rhSTC and phosphonoformic acid. Taken together, our findings indicate that STC1 inhibits longitudinal bone growth directly at the growth plate. Such growth inhibition, likely mediated by an increased chondrocyte phosphate uptake, results from suppressed chondrocyte proliferation, hypertrophy/differentiation, and matrix synthesis and by increased apoptosis. Last, the expression of both STC1 and its binding site in the growth plate would support an autocrine/paracrine role for this growth factor in the regulation of growth plate chondrogenesis. Stanniocalcin (STC)2 is a glycoprotein first identified as a secretory product of the corpuscles of Stannius, an endocrine gland unique to bony fish (1, 2). The primary function of STC in fish is to prevent hypercalcemia (3) by inhibiting calcium uptake by the gills and gut and stimulating phosphate reabsorption by the kidneys (1, 4).The mammalian homolog of STC (STC1) has been found in humans, rats, and mice (5-7). Human and mouse STC1 proteins are closely related to each other (98% amino acid identity) and share 80% amino acid identity with fish STC (5). Compared with fish STC, STC1 seems to have a preferential effect on phosphate metabolism than on calcium metabolism (8, 9), with evidence suggesting that sodium-dependent P i (NaP i ) transporter(s) may be a target of STC1 activity (10). Although fish STC is primarily expressed in one organ (the corpuscle of Stannius), mammalian STC1 is virtually ubiquitous. The distribution of STC protein and/or mRNA in multiple organs such as kidney, intestine, heart, thyroid, lung, placenta, brain (11-15), and bone (with virtually undetectable serum levels) (11) would suggest a paracrine rather than an endocrine ...

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Stanniocalcin 1 (STC1) Protein and mRNA Are Developmentally Regulated During Embryonic Mouse Osteogenesis: the Potential of STC1 as an Autocrine/Paracrine Factor for Osteoblast Development and Bone Formation

Cited by 34 publications

References 37 publications

Strain Reduction of Human Gingival Fibroblasts Induces the ATP Pathway

Strain Reduction of Human Gingival Fibroblasts Induces the ATP Pathway

The Murine Stanniocalcin 1 Gene Is Not Essential for Growth and Development

Stanniocalcin 1 Acts as a Paracrine Regulator of Growth Plate Chondrogenesis

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