Cobalt protoporphyrin induces differentiation of monocytic THP-1 cells through regulation of cytoplasmic Ref-1-related NADPH oxidase activity

Song, Ju Dong; Lee, Sang Kwon; Park, Si Eun; Kim, Kang Mi; Kim, Koanhoi; Park, Yeong Min; Park, Young Chul

doi:10.3892/ijmm.2011.736

Cited by 1 publication

(1 citation statement)

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“…CoPP exerts inhibitory effects on differentiation of macrophages into dendritic cells (Chauveau et al, 2005;Mashreghi et al, 2008). In contrast to the inhibitory effects, CoPP promotes the differentiation from human monocyte THP-1 into macrophage-like cells that express several differentiation maker proteins (Song et al, 2011). Given that modulation of CoPP in macrophage differentiation, it remains unknown whether CoPP inhibits OCL differentiation or not.…”

Section: Introductionmentioning

confidence: 99%

Cobalt protoporphyrin represses osteoclastogenesis through blocking multiple signaling pathways

et al. 2015

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Abstract.Cobalt protoporphyrin (CoPP) is a metallo-protoporphyrin that works as a powerful inducer of heme oxigenase-1 (HO-1) in various tissues and cells. Our recent studies have demonstrated that induction of HO-1 by several reagents inhibited differentiation and activation of osteoclasts (OCLs), which are multinucleated bone resorbing cells. However, the effects of CoPP on osteoclastogenesis remain to be elucidated. In this study, we report that CoPP inhibits receptor activator of nuclear factor κB ligand (RANKL)-induced OCL formation in a dose dependent manner. Importantly, CoPP had little cytotoxicity, but rather enhanced cell proliferation of OCLs. CoPP suppressed the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1) as well as those of OCLs markers such as Src and cathepsin K, which are transcriptionally regulated by NFATc1 in mature OCLs. Western blot analyses also showed that CoPP abolished RANKL-stimulated phosphorylation of several major signaling pathways such as IκB, Akt, ERK, JNK and p38 MAPKs in OCL precursor cells. Thus, our results show that CoPP represses osteoclastogenesis through blocking multiple signaling pathways.

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Section: Introductionmentioning

confidence: 99%