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27 results on '"Gautvik, Vigdis T."'

3. Mechanical-Stress-Related Epigenetic Regulation of ZIC1 Transcription Factor in the Etiology of Postmenopausal Osteoporosis

Author

Datta, Harish K, Kringen, Marianne K, Tuck, Stephen P, Salpingidou, Georgia, Olstad, Ole K, Gautvik, Kaare M, Cockell, Simon J, Gautvik, Vigdis T, Prediger, Michael, Wu, Jun Jie, Birch, Mark A, Reppe, Sjur, Datta, Harish K [0000-0002-4729-9340], Tuck, Stephen P [0000-0001-5060-4214], Cockell, Simon J [0000-0002-6831-9806], Reppe, Sjur [0000-0002-4330-5379], and Apollo - University of Cambridge Repository

Subjects
Mechanical stress, ZIC1 transcription factor, bone, Catalysis, Epigenesis, Genetic, Ilium, Inorganic Chemistry, Bone Density, Animals, Humans, osteoporosis, mechanical stress, epigenetic, RNA, Messenger, Physical and Theoretical Chemistry, Molecular Biology, Osteoporosis, Postmenopausal, Spectroscopy, Lumbar Vertebrae, Organic Chemistry, Epigenetic, General Medicine, Rats, Computer Science Applications, Osteoporosis, Female, Stress, Mechanical, Transcription Factors
Abstract

Mechanical loading exerts a profound influence on bone density and architecture, but the exact mechanism is unknown. Our study shows that expression of the neurological transcriptional factor zinc finger of the cerebellum 1 (ZIC1) is markedly increased in trabecular bone biopsies in the lumbar spine compared with the iliac crest, skeletal sites of high and low mechanical stress, respectively. Human trabecular bone transcriptome analyses revealed a strong association between ZIC1 mRNA levels and gene transcripts characteristically associated with osteoblasts, osteocytes and osteoclasts. This supposition is supported by higher ZIC1 expression in iliac bone biopsies from postmenopausal women with osteoporosis compared with age-matched control subjects, as well as strongly significant inverse correlation between ZIC1 mRNA levels and BMI-adjusted bone mineral density (BMD) (Z-score). ZIC1 promoter methylation was decreased in mechanically loaded vertebral bone compared to unloaded normal iliac bone, and its mRNA levels correlated inversely with ZIC1 promoter methylation, thus linking mechanical stress to epigenetic control of gene expression. The findings were corroborated in cultures of rat osteoblast progenitors and osteoblast-like cells. This study demonstrates for the first time how skeletal epigenetic changes that are affected by mechanical forces give rise to marked alteration in bone cell transcriptional activity and translate to human bone pathophysiology.

Published
2022

4. Mechanical-Stress-Related Epigenetic Regulation of ZIC1 Transcription Factor in the Etiology of Postmenopausal Osteoporosis

Author

Datta, Harish K., primary, Kringen, Marianne K., additional, Tuck, Stephen P., additional, Salpingidou, Georgia, additional, Olstad, Ole K., additional, Gautvik, Kaare M., additional, Cockell, Simon J., additional, Gautvik, Vigdis T., additional, Prediger, Michael, additional, Wu, Jun Jie, additional, Birch, Mark A., additional, and Reppe, Sjur, additional

Published
2022
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6. Additional file 1 of Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults

Author

Gautvik, Kaare M., Olstad, Ole K., Raue, Ulrika, Gautvik, Vigdis T., Kvernevik, Karl J., Utheim, Tor P., Ravnum, Solveig, Kirkegaard, Camilla, Wiig, Håvard, Jones, Garan, Pilling, Luke C., Trappe, Scott, Raastad, Truls, and Reppe, Sjur

Abstract

Addiitional file 1: Figure S1. Comparison of transcript signal levels between os ilium–associated muscle and thigh muscle. Figure S2. Genes within the Diseases and Function category Vasculogenesis with increased (red) or reduced (green) expression end vs start of the training period in elderly as compared to young. Table S1. Common annotated genes changed in elderly in both Oslo and BSU cohorts at Q-value

Published
2022
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9. Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture, Studied in Weight‐Bearing and Non–Weight‐Bearing Human Bone

Author

Gautvik, Kaare M, primary, Günther, Clara‐Cecilie, additional, Prijatelj, Vid, additional, Medina‐Gomez, Carolina, additional, Shevroja, Enisa, additional, Rad, Leila Heidary, additional, Yazdani, Mazyar, additional, Lindalen, Einar, additional, Valland, Haldor, additional, Gautvik, Vigdis T, additional, Olstad, Ole K, additional, Holden, Marit, additional, Rivadeneira, Fernando, additional, Utheim, Tor P, additional, and Reppe, Sjur, additional

Published
2020
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11. Methylation of Bone SOST, Its mRNA, and Serum Sclerostin Levels Correlate Strongly With Fracture Risk in Postmenopausal Women

Author

Reppe, Sjur, primary, Noer, Agate, additional, Grimholt, Runa M, additional, Halldórsson, Bjarni V, additional, Medina‐Gomez, Carolina, additional, Gautvik, Vigdis T, additional, Olstad, Ole Kristoffer, additional, Berg, Jens Petter, additional, Datta, Harish, additional, Estrada, Karol, additional, Hofman, Albert, additional, Uitterlinden, André G, additional, Rivadeneira, Fernando, additional, Lyle, Robert, additional, Collas, Philippe, additional, and Gautvik, Kaare M, additional

Published
2015
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17. Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice

Author

Nissen-Meyer, Lise Sofie Haug, primary, Jemtland, Rune, additional, Gautvik, Vigdis T., additional, Pedersen, Mona E., additional, Paro, Rita, additional, Fortunati, Dario, additional, Pierroz, Dominique D., additional, Stadelmann, Vincent A., additional, Reppe, Sjur, additional, Reinholt, Finn P., additional, Del Fattore, Andrea, additional, Rucci, Nadia, additional, Teti, Anna, additional, Ferrari, Serge, additional, and Gautvik, Kaare M., additional

Published
2007
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21. Isolation and characterization of two biologically active O-glycosylated forms of human parathyroid hormone produced in Saccharomyces cerevisiae. Identification of a new motif for O-glycosylation

Author

OLSTAD, Ole Kristoffer, primary, REPPE, Sjur, additional, GABRIELSEN, Odd S., additional, HARTMANIS, Maris, additional, BLINGSMO, Ola R., additional, GAUTVIK, Vigdis T., additional, HAFLAN, Anne Karine, additional, CHRISTENSEN, Terje B., additional, OYEN, Tordis B., additional, and GAUTVIK, Kaare M., additional

Published
1992
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25. Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice

Author

Nissen-Meyer, Lise Sofie Haug, Jemtland, Rune, Gautvik, Vigdis T., Pedersen, Mona E., Paro, Rita, Fortunati, Dario, Pierroz, Dominique D., Stadelmann, Vincent A., Reppe, Sjur, Reinholt, Finn P., Del Fattore, Andrea, Rucci, Nadia, Ferrar, Serge, and Gautvik, Kaar M.

Abstract

The transcription factor Sox4 is vital for fetal development, as Sox4–/– homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/– mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (μCT), histomorphometry and biomechanical testing of Sox4+/– bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/– mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/– mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4+/– cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/– mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2.

26. Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice.

Author

Nissen-Meyer, Lise Sofie Haug, Jemtland, Rune, Gautvik, Vigdis T., Pedersen, Mona E., Paro, Rita, Fortunati, Dario, Pierroz, Dominique D., Stadelmann, Vincent A., Reppe, Sjur, Reinholt, Finn P., Del Fattore, Andrea, Rucci, Nadia, Teti, Anna, Ferrari, Serge, and Gautvik, Kaare M.

Subjects
OSTEOPENIA, BONE growth, OSTEOCLASTS, TRANSCRIPTION factors, BONE remodeling, BONE density, LABORATORY mice
Abstract

The transcription factor Sox4 is vital for fetal development, as Sox4-/- homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/- mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (µCT), histomorphometry and biomechanical testing of Sox4+/- bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/- mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/- mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4+/- cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/-- mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2. [ABSTRACT FROM AUTHOR]

Published
2007

27. Molecular heterogeneity in human osteosarcoma demonstrated by enriched mRNAs isolated by directional tag PCR subtraction cloning.

Author

Olstad OK, Gautvik VT, Reppe S, Rian E, Jemtland R, Ohlsson C, Bruland OS, and Gautvik KM

Subjects
Animals, Biopsy, Blotting, Northern, Bone Neoplasms metabolism, DNA, Complementary genetics, DNA, Neoplasm genetics, Gene Expression Profiling, Humans, Mice, Mice, Nude, Nucleic Acid Hybridization, Osteosarcoma metabolism, Polymerase Chain Reaction methods, RNA, Messenger biosynthesis, Transplantation, Heterologous, Tumor Cells, Cultured, Bone Neoplasms genetics, Osteosarcoma genetics, RNA, Messenger genetics
Abstract

Directional tag PCR subtractive hybridization was applied to construct a cDNA library generated from three different human osteosarcoma (OS) target cell lines (OHS, SaOS-2 and KPDXM) from which normal osteoblast (NO) sequences were subtracted. After two consecutive subtractive steps more than 98% of the common mRNAs species were depleted, leading to effective enrichment of the remaining target sequences. After differential screening of 960 clones, 81 candidates were further studied by Northern blot analysis and 73 represented separate mRNA species. Fifty-three of these showed enriched mRNA levels, of which 36 represented known and 17 not previously published cDNAs or EST sequences. The mRNAs showed a 1.4- to 504-fold enrichment compared to the mRNA levels in NO cells. The known mRNAs are: Ribosomal protein S11, KSP-37, Tethering factor SEC34, FXYD6, Alpha enolase, G-s-alpha, GPR85, DAF, RPL35A, GIF, TAPA-1, ANAPC11, DCI, hsp27, MRPS7 homolog, eIF p110 subunit, DPH2L, HMG-14, FB1 protein, chondroitin-6-sulphonase, calgizzarin, RNA polymerase II subunit, RPL13A, DHS, gp96, HHP2, acidic ribosomal phosphoprotein P2, ANT-2, ARF1, AFG3L2, SKD3, phosphoglucoisomerase, GST pi, CKI gamma 2, DNA polymerase delta small subunit and TRAP delta. Sections of human osteosarcoma biopsies and a xenograft were studied by in situ analysis. Seven cDNAs highly expressed in Northern blot analysis were tested. Their in situ expression differed between the xenograft and human sections as did that of collagen I. In the xenograft made from one of the target cell lines (OHS), a fair to strong representation of 3 cloned mRNAs was observed while collagen I mRNA was not detectable. We conclude that the molecular heterogeneity of these tumors is considerable. These results ought to have implications for future work to describe phenotypic subtypes with the aim of improving the diagnosis of human osteosarcomas.

Published
2003

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