The Journal of biological chemistry, 2016-03, Vol.291 (13), p.6754-6771
2016
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate
- Ist Teil von
- The Journal of biological chemistry, 2016-03, Vol.291 (13), p.6754-6771
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). 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 the Tet1/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 resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M115.678235Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4807263
- Format
- –
- Schlagworte
- Activating Transcription Factor 4 - genetics, Activating Transcription Factor 4 - metabolism, Animals, Apoptosis - drug effects, Apoptosis - genetics, bone, Bone Density Conservation Agents - pharmacology, Bone Resorption - genetics, Bone Resorption - metabolism, Bone Resorption - pathology, Bone Resorption - prevention & control, Caspase 8 - genetics, Caspase 8 - metabolism, Cell Biology, Cell Differentiation, Collagen Type I - genetics, Collagen Type I - metabolism, Core Binding Factor Alpha 1 Subunit - genetics, Core Binding Factor Alpha 1 Subunit - metabolism, DNA Methylation, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Epigenesis, Genetic, epigenetics, Female, Humans, Isothiocyanates - pharmacology, Mice, Mice, Inbred C57BL, osteoblast, Osteoblasts - cytology, Osteoblasts - drug effects, Osteoblasts - metabolism, osteoclast, Osteoclasts - drug effects, Osteoclasts - metabolism, Osteoclasts - pathology, osteoporosis, Osteoporosis - drug therapy, Osteoporosis - genetics, Osteoporosis - metabolism, Osteoporosis - pathology, Ovariectomy, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, RANK Ligand - genetics, RANK Ligand - metabolism, Signal Transduction, Sp7 Transcription Factor, Transcription Factors - genetics, Transcription Factors - metabolism, X-Ray Microtomography