Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate
Thaler R, Maurizi A, Roschger P, Sturmlechner I, Khani F, Spitzer S, Rumpler M, Zwerina J, Karlic H, Dudakovic A, Klaushofer K, Teti A, Rucci N, Varga F, van Wijnen AJ
The Journal of biological chemistry · 58 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Animales
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Gobierno
- NIAMS NIH HHS
- Gobierno
- Austrian Science Fund FWF
- Subvenciones
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR049069); National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 049069)
Según 3 financiadores declarados.
Publicación
- Publicado
- 2016-01-13 · J Biol Chem · vol. 291 · número 13 · págs. 6754–6771
- Editorial
- Elsevier BV
- Citado
- 73 citas · más que el 95% de estudios similares · 4.3× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 74 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Macrophage Migration Inhibitory Factor · Biochemical Acid Research Studies
- Palabras clave
- Sulforaphane, Anabolism, Epigenetics, Isothiocyanate, Chemistry, Biochemistry, Gene
- MeSH
- osteoclasts, osteoblasts, animals, mice, inbred c57bl, humans, mice, osteoporosis, bone resorption, isothiocyanates, sulfoxides, collagen type i, dioxygenases, dna-binding proteins, proto-oncogene proteins, transcription factors, ovariectomy, signal transduction, apoptosis, cell differentiation, dna methylation, epigenesis, genetic, female, bone density conservation agents, core binding factor alpha 1 subunit, activating transcription factor 4, caspase 8, rank ligand, x-ray microtomography, sp7 transcription factor, collagen type i, alpha 1 chain
15 autores
- Roman Thaler🇺🇸🇦🇹Mayo Clinic; Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Antonio Maurizi🇮🇹University of L'Aquila
- Paul Roschger🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Ines Sturmlechner🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Farzaneh Khani🇺🇸Mayo Clinic; Mayo Clinic in Arizona
- Silvia G. Spitzer🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Monika Rumpler🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Jochen Zwerina🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Heidrun Karlic🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Amel Dudakovic🇺🇸Mayo Clinic; Mayo Clinic in Arizona
- Klaus Klaushofer🇦🇹Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Anna Maria Teti🇮🇹University of L'Aquila
- Nadia Rucci🇮🇹 · autor de correspondenciaUniversity of L'Aquila
- Franz Varga🇦🇹 · autor de correspondenciaHanusch Hospital; Ludwig Boltzmann Institute of Osteology
- André J. van Wijnen🇺🇸 · autor de correspondenciaMayo Clinic; Mayo Clinic in Arizona; Mayo Clinic in Florida
Resumen
El texto original del estudio, en el idioma en que se publicó.
Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of theTet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorptionin vivo Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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