Hydrogen peroxide-induced poly(ADP-ribosyl)ation regulates osteogenic differentiation-associated cell death

Robaszkiewicz, Agnieszka; Erdélyi, Katalin; Kovács, Katalin; Kovács, István; Bai, Péter; Rajnavölgyi, Éva; Virág, László

doi:10.1016/j.freeradbiomed.2012.08.567

Cited by 41 publications

(51 citation statements)

References 42 publications

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“…Chorion-derived mesenchymal stem cells (MSC) were isolated from human placentas (as approved by the regional research ethics committee under license number DEOEC-RKEB-2946-2009) and phenotyped on the basis of surface antigen pattern using cell staining with appropriate antibodies combined with flow cytometric analysis (Becton Dickinson BD FACSCalibur and BD Multiset Software v3.0x for Mac OS X) as described previously [7]. Only cells positive for CD73, CD90, CD105, and CD166 and negative for CD34, CD45, vWF, and HLA-G were used in the experiments.…”

Section: Isolation and Phenotyping Of Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Cell culture and differentiation SAOS-2 human osteosarcoma cells and chorion-derived mesenchymal stem cells were cultured and differentiated as previously desribed [7].…”

Section: Isolation and Phenotyping Of Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Osteogenic differentiation is accompanied by massive cell death with the majority of differentiating cells undergoing apoptosis [6,7]. The identity and regulation of the cell death subroutine mediating osteogenic differentiation-coupled cell death, however, have not yet been completely characterized.…”

Section: Introductionmentioning

confidence: 99%

“…The identity and regulation of the cell death subroutine mediating osteogenic differentiation-coupled cell death, however, have not yet been completely characterized. Production of reactive oxygen species has been shown to accompany osteogenesis [8,9] and our group has established the contribution of the hydrogen peroxide-induced poly(ADP-ribose) polymerase-1 (PARP1) pathway to osteogenic differentiation and related cell death [7]. Poly (ADP-ribosyl)ation is a protein modification catalyzed by some members of the PARP enzyme family.…”

Section: Introductionmentioning

confidence: 99%

“…Since we have previously demonstrated the lack of AIF translocation during osteogenic differentiation-coupled cell death [7], here we set out to investigate the role of MAP kinase signaling and compromised cellular energetics as possible mediators of PARP1-dependent cell death during osteogenic differentiation. We show that while all three MAP kinases become activated during the course of osteogenic differentiation, inhibition or silencing of PARP1 only suppresses the activation of p38, while Erk1/2 activation was augmented and JNK activation was not affected.…”

Section: Introductionmentioning

confidence: 99%

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The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

Robaszkiewicz

Valkó

Kovács

et al. 2014

Free Radical Biology and Medicine

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a b s t r a c tOsteogenic differentiation is a multistep process regulated by a diverse set of morphogenic and transcription factors. Previously we identified endogenous hydrogen peroxide-induced poly(ADP-ribose) polymerase-1 (PARP1) activation as a mediator of osteodifferentiation and associated cell death. Here we set out to investigate whether or not activation of PARP1 is dependent on DNA breaks and how PARP1 mediates cell death during osteodifferentiation of mesenchymal stem cells and SAOS-2 cells. Here we show that the MAP kinases p38, JNK, and ERK1/2 become activated during the differentiation process. However, only p38 activation depended both on hydrogen peroxide production and on PARP1 activation as the hydrogen peroxide decomposing enzyme catalase, the PARP inhibitor PJ34, and the silencing of PARP1 suppressed p38 activation. Inhibition of p38 suppressed cell death and inhibited osteogenic differentiation (calcium deposition, alkaline phosphatase activity, and marker gene expression) providing further support for the close coupling of osteodifferentiation and cell death. Metabolic collapse appears to be central in the hydrogen peroxide-PARP1-p38 pathway as silencing PARP1 or inhibition of p38 prevented differentiation-associated loss of cellular NAD, inhibition of mitochondrial respiration, and glycolytic activity. We also provide evidence that endogenous hydrogen peroxide produced by the differentiating cells is sufficient to cause detectable DNA breakage. Moreover, p38 translocates from the cytoplasm to the nucleus where it interacts and colocalizes with PARP1 as detected by immunoprecipitation and immunofluorescence, respectively. In summary, hydrogen peroxide-induced PARP1 activation leads to p38 activation and this pathway is required both for the successful completion of the differentiation process and for the associated cell death.

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Section: Isolation and Phenotyping Of Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Cell culture and differentiation SAOS-2 human osteosarcoma cells and chorion-derived mesenchymal stem cells were cultured and differentiated as previously desribed [7].…”

Section: Isolation and Phenotyping Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

Robaszkiewicz

Valkó

Kovács

et al. 2014

Free Radical Biology and Medicine

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Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

Liu

Han

Werner

et al. 2017

Journal of Bone and Mineral Research

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Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a main determinant of low cortical but not trabecular bone mass.

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The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis

Liu

et al. 2022

Cell. Mol. Life Sci.

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Hydrogen peroxide-induced poly(ADP-ribosyl)ation regulates osteogenic differentiation-associated cell death

Cited by 41 publications

References 42 publications

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis

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