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 · 57 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Government
- NIAMS NIH HHS
- Government
- Austrian Science Fund FWF
- Grants
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR049069); National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 049069)
Based on 3 listed funder(s).
Publication
- Published
- 2016-01-13 · J Biol Chem · vol. 291 · issue 13 · pp. 6754–6771
- Publisher
- Elsevier BV
- Cited
- 73 citations · more than 95% of similar papers · 4.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 74 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Macrophage Migration Inhibitory Factor · Biochemical Acid Research Studies
- Keywords
- 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 authors
From US, AT, IT
- Roman ThalerMayo Clinic; Hanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Antonio MauriziUniversity of L'Aquila
- Paul RoschgerHanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Ines SturmlechnerHanusch Hospital; Ludwig Boltzmann Institute of Osteology
- Farzaneh KhaniMayo Clinic; Mayo Clinic in Arizona
- Silvia G. SpitzerHanusch Hospital; Ludwig Boltzmann Institute of Osteology
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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