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

Autor: Datta HK; Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.; Blood Sciences, South Tees Hospitals NHS Foundation Trust, Middlesbrough TS4 3BW, UK., Kringen MK; Center for Psychopharmacology, Diakonhjemmet Hospital, 0319 Oslo, Norway., Tuck SP; Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK., Salpingidou G; Department of Engineering, Faculty of Science, Durham University, Durham DH1 3 LE, UK., Olstad OK; Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway., Gautvik KM; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway., Cockell SJ; School of Biomedical, Nutritional and Sport Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Gautvik VT; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway., Prediger M; Blood Sciences, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne NE2 4HH, UK., Wu JJ; Department of Engineering, Faculty of Science, Durham University, Durham DH1 3 LE, UK., Birch MA; Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK., Reppe S; Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway.; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway.; Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0424 Oslo, Norway.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Mar 09; Vol. 23 (6). Date of Electronic Publication: 2022 Mar 09.
DOI: 10.3390/ijms23062957
Abstrakt: 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.
Databáze: MEDLINE
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