Background A great deal numbers of histone-deacetylase inhibitors (HDACs) have been well recognized as potential anti-cancer drugs. Inhibition of HDAC induces temporal transcription or epigenetic control, regulating many different biological responses.
Objectives Due to this notable feature associated with HDACs it occurs to a rational concept that HDAC may be also involved in differentiation osteoblasts (OB). Consistent with this concept we have previously reported that MS-275, a HDAC, affected differentiation of OB via induction of a DNA helicase called Dhs36. Here, we investigated the osteogenic effect of suberoylanilide hydroxamic acid (SAHA).
Methods The effects of SAHA on osteoblast differentiation were examined in 6XOSE-Luc reporter assay and alkaline phosphatase activity (ALP) assay in activity and immunoprecipitation assay with Runx2. The osteogenic activity of SAHA was determined in vivo in a sRANKL-induced osteoporotic model.
Results SAHA was able to augment transcriptional activity of Runx2 in a dose-dependent manner shown by a 6XOSE-Luc reporter assay. SAHA by itself was unable to induce ALP, however, SAHA increased ALP activity synergized with BMP-2. The degree of acetylation of Runx2 was increased with the treatment of SAHA, indicating that the transcriptional activity associated with Runx2 might depend on stabilization of an acetylated Runx2. Also, SAHA showed the inhibition of bone loss in sRANL-induced osteoporotic mice model.
Conclusions Our study shows an intriguing osteogenic potential of SAHA in a BMP-2 dependent manner, suggesting that SAHA could be used at lower doses along with BMP-2 to treat osteoporosis.
Kim et al. Histone Deacetylase Inhibitor MS-275 Stimulates Bone Formation in Part by Enhancing Dhx36-Mediated TNAP Transcription. J Bone Miner Res. 2011, 26:2161-2173.
Acknowledgements This work was supported by a grant of the Korean Health
Technology R&D Project, Ministry of Health & Welfare (A120850).
Disclosure of Interest None declared