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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Background: Protein methylation has important role in regulating diverse cellular responses, including differentiation, by affecting protein activity, stability, and interactions. AZ505 is an inhibitor of the SET and MYND domain-containing protein 2 lysine methylase. In this study, we investigated the effect of AZ505 on osteoblast and osteoclast differentiation in vitro and evaluated the effect of AZ505 in vivo on the long bones in mice. Methods: Osteoblast differentiation was assessed by alkaline phosphatase (ALP) and Alizarin red staining after culturing calvarial preosteoblasts in an osteogenic medium. Osteoclast differentiation was analyzed by tartrate-resistant acid phosphatase (TRAP) staining in bone marrow-derived macrophages cultured with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). For in vivo experiments, mice were intraperitoneally injected with AZ505 and femurs were examined by micro-computed tomography. Results: AZ505 increased ALP and Alizarin red staining in cultured osteoblasts and the expression of osteoblast marker genes, including Runx2 and osteocalcin. AZ505 resulted in decreased TRAP-staining of osteoclasts and expression of c-Fos and nuclear factor of activated T cells transcription factors and osteoclast marker genes, including cathepsin K and dendritic cell-specific transmembrane protein. Unexpectedly, in vivo administration of AZ505 markedly decreased the trabecular bone mass of femurs. In support of this catabolic result, AZ505 strongly upregulated RANKL expression in osteoblasts. Conclusions: The results indicate that AZ505 has a catabolic effect on bone metabolism in vivo despite its anabolic effect in bone cell cultures. The findings indicate that cell culture data should be extrapolated cautiously to in vivo outcomes for studying bone metabolism.
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참고문헌 (34)
참고문헌 신청
Matlock A. Jeffries / 2020 / The Development of Epigenetics in the Study of Disease Pathogenesis / Advances in Experimental Medicine and Biology 1253:57~94
조영단 / 2018 / Trans-differentiation via Epigenetics: A New Paradigm in the Bone Regeneration / 대한골대사학회지 25(1):9~13
Xin Yi / 2019 / Histone methyltransferase SMYD2: ubiquitous regulator of disease / Clinical Epigenetics 11(1):112
Naveen Parmar / 2020 / Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization / The Journal of Immunology 204(10):2762~2778
Ryuji Hamamoto / 2015 / Critical roles of non-histone protein lysine methylation in human tumorigenesis / Nature Reviews Cancer 15(2):110~124
조영단 / 2018 / Trans-differentiation via Epigenetics: A New Paradigm in the Bone Regeneration / 대한골대사학회지 25(1):9~13
Xin Yi / 2019 / Histone methyltransferase SMYD2: ubiquitous regulator of disease / Clinical Epigenetics 11(1):112
Naveen Parmar / 2020 / Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization / The Journal of Immunology 204(10):2762~2778
Ryuji Hamamoto / 2015 / Critical roles of non-histone protein lysine methylation in human tumorigenesis / Nature Reviews Cancer 15(2):110~124
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