BoneKEy Reports | BoneKEy Watch
Inhibiting histone deacetylases could stimulate fracture repair
DOI:10.1038/bonekey.2013.193
Hu et al. investigated whether histone deacetylases (Hdacs) impact on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts, a process regulated by bone morphogenetic protein 9 (BMP9).
PCR analysis showed that an MSC cell line expressed all Hdacs, with Hdacs 2 and 8 showing the highest levels of expression. BMP9 upregulated all Hdacs, but 3, 5, 6 and 11 were induced significantly within 48–72 h. Use of trichostatin A (TSA), a potent Hdac inhibitor, enhanced osteogenic markers that are known to be induced by BMP9 – such as the early marker alkaline phosphatase and the late markers osteocalcin and osteopontin. Moving from cell culture to limb explants from mouse embryos, the authors then demonstrated that TSA increased bone formation as mediated by BMP9.
They suggest that BMP9 has a more significant role in bone development than previously realized and that Hdacs impact on osteogenic signaling mediated by BMP9 through a negative feedback loop. They speculate that inhibiting Hdacs in vivo could enhance healing of bone fractures.
Editor’s comment: Simple Hdac inhibition was able to promote BMP9 activity in cell and organ culture. This interesting approach needs testing in multiple animal models, but the concept of increasing endogenous BMP9 function is appealing.
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