MITF and PU.1 Recruit p38 MAPK and NFATc1 to Target Genes during Osteoclast Differentiation

Sharma, Sudarshana M.; Bronisz, Agnieszka; Hu, Rong; Patel, Krupen; Mansky, Kim C.; Sif, Saı̈d; Ostrowski, Michael C.

doi:10.1074/jbc.m609723200

Cited by 159 publications

(187 citation statements)

References 33 publications

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“…In addition, MITF is a sensitive and specific marker for melanoma, a highly chemotherapy-resistance neoplasm (McGill et al, 2002). MITF was demonstrated to promote the occupancy of osteoclast target promoters (activated form of MITF) and regulation of co-recruitment of chromatin-remodelling complex (Sharma et al, 2007). The up-regulation of MITF gene suggests that Aloe emodin may affect tissue remodelling of U87 cells.…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Haris

Ismail²,

Idris³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 µg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.

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Section: Discussionmentioning

confidence: 99%

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Haris

Ismail²,

Idris³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…It was shown that the expression of dominant-negative forms of p38 MAPK and MKK6 in RAW264.7 cells inhibited RANKL-induced differentiation of RAW264.7 cells into osteoclasts (Matsumoto et al 2000). Moreover, addition of luteolin to osteoclast cultures strongly inhibited the expression of NFATc1, which is a key transcription factor for the expressions of TRAP and other osteoclastogenesis-associated genes (Ikeda et al 2004;Matsumoto et al 2004;Sharma et al 2007). Therefore, the effects of luteolin on osteoclastogenesis are probably mediated by ATF2, downstream of p38 MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of luteolin on osteoclast differentiation and function

et al. 2009

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Osteoclasts are multinucleated cells that play a crucial role in bone resorption, and are formed by the fusion of mononuclear osteoclasts derived from osteoclast precursors of the macrophage lineage. Compounds that specifically target functional osteoclasts would be ideal candidates for anti-resorptive agents for clinical applications. In the present study, we investigated the effects of luteolin, a flavonoid, on the regulation of receptor activator of nuclear factorjB ligand (RANKL)-induced osteoclastogenesis, functions and signaling pathway. Addition of luteolin to a coculture system of mouse bone marrow cells and ST2 cells in the presence of 10 -8 M 1a,25(OH) 2 D 3 caused significant inhibition of osteoclastogenesis. Luteolin had no effects on the 1a,25(OH) 2 D 3 -induced expressions of RANKL, osteoprotegerin and macrophage colony-stimulating factor mRNAs. Next, we examined the direct effects of luteolin on osteoclast precursors using bone marrow macrophages and RAW264.7 cells. Luteolin completely inhibited RANKL-induced osteoclast formation. Moreover, luteolin inhibited the bone resorption by mature osteoclasts accompanied by the disruption of their actin rings, and these effects were reversely induced by the disruption of the actin rings in mature osteoclasts. Finally, we found that luteolin inhibited RANKLinduced osteoclastogenesis through the suppression of ATF2, downstream of p38 MAPK and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) expression, respectively. Taken together, the present results indicate that naturally occurring luteolin has inhibitory activities toward both osteoclast differentiation and functions through inhibition of RANKL-induced signaling pathway as well as actin ring disruption, respectively.

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“…In addition, PU.1 and microphthalmia-associated transcription factor MITF, a basic helix-loop-helix-leucine zipper protein, collaborate to increase an expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation [41,42]. They recruit p38 mitogen activated protein kinase and Nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) to target genes during osteoclast differentiation [43].…”

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

Molecular Understanding of Osteoclast Differentiation and Physiology

Lee

2010

Endocrinol Metab

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MITF and PU.1 Recruit p38 MAPK and NFATc1 to Target Genes during Osteoclast Differentiation

Cited by 159 publications

References 33 publications

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Inhibitory effect of luteolin on osteoclast differentiation and function

Molecular Understanding of Osteoclast Differentiation and Physiology

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