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Abstract Title:

Allyl sulfide promotes osteoblast differentiation and bone density via reducing mitochondrial DNA release mediated Kdm6b/H3K27me3 epigenetic mechanism.

Abstract Source:

Biochem Biophys Res Commun. 2021 Mar 5 ;543:87-94. Epub 2021 Feb 6. PMID: 33556823

Abstract Author(s):

Jyotirmaya Behera, Jessica Ison, Hitesh Rai, Neetu Tyagi

Article Affiliation:

Jyotirmaya Behera

Abstract:

Age-associated bone loss or osteoporosis is a common clinical manifestation during aging (AG). The mechanism underlying age-associated osteoblast dysfunction induced by oxidative damage in the mitochondria and loss of bone density remains elusive. Here, we demonstrated the effect of allyl sulfide (AS), a natural organosulfur compound, on mitochondrial (mt) function in bone marrow-derived mesenchymal stem cells (BMMSCs) and bone density in AG mice. The data demonstrate that AS treatment in AG mice promotes BMMSCs differentiation and mineralization via inhibition of mitochondrial oxidative damage. The data also indicate that AG related mito-damage was associated with reduced mitochondrial biogenesis and oxidative phosphorylation, and release of a greater concentration of mtDNA. Furthermore, the data showed that mtDNA caused histone H3K27 demethylase inhibition, KDM6B, and subsequent inflammation by unbalancing mitochondrial redox homeostasis. KDM6B overexpression in AG BMMSCs or AS administration in AG mice restores osteogenesis and bone density in vitro and in vivo. Mechanistically, AS or the mitochondrial-specific antioxidant Mito-TEMPO increased KDM6B expression and upregulated the expression of Runx2 in BMMSCs, probably via epigenetic inhibition of H3K27me3 methylation at the promoter. These data uncover the previously undefined role ofAS mediated prevention of mtDNA release, promoting osteogenesis and bone density via an epigenetic mechanism. Therefore, AS could be a potential drug target for the treatment of aging-associated osteoporosis.

Study Type : Animal Study, In Vitro Study
Additional Links
Pharmacological Actions : Osteoprotective : CK(971) : AC(351)

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