Peroxiredoxin II Negatively Regulates Lipopolysaccharide-Induced Osteoclast Formation and Bone Loss<i>via</i>JNK and STAT3

Park, Hyo Jung; Noh, A Long Sae Mi; Kang, Ju‐Hee; Sim, Jung-Sun; Lee, Dong Seok; Yim, Mijung

doi:10.1089/ars.2013.5748

Cited by 45 publications

(32 citation statements)

References 61 publications

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“…Moreover, either inhibition of JNK1 activity by a specific inhibitor or knockdown of JNK1 by RNA interference significantly decreased osteoclast formation (9). Similar findings were also reported by other investigations (13)(14)(15)(16). Consistently, the JNK kinase assay showed that JNK1 was specifically activated by RANKL (12).…”

supporting

confidence: 83%

JNK1 regulates RANKL‐induced osteoclastogenesis via activation of a novel Bcl‐2‐Beclin1‐autophagy pathway

Wang

et al. 2019

FASEB j.

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JNK1 plays an important role in osteoclastogenesis in response to the osteoclastogenic cytokine receptor activator for nuclear factor‐κB ligand (RANKL). JNK1 is widely accepted as an autophagy regulator under stress conditions. However, the role of JNK1‐mediated autophagy in osteoclastogenesis remains largely unknown. In the current study, our data showed that JNK1 inhibition by a pharmacological inhibitor or RNA interference significantly reduced the autophagic response induced by RANKL in osteoclast precursors (OCPs) derived from bone marrow‐derived macrophages. Overexpression of the key autophagy protein Beclin1 rescued autophagy deficiency and osteoclastogenesis in the presence of a JNK inhibitor (SP600125). In contrast, JNK activator (anisomycin)‐induced autophagy was blocked by Beclin1 knockdown in OCPs. In addition, JNK1 inhibition increased apoptosis and blocked autophagy, whereas overexpression of Beclin1 reversed the enhanced apoptosis induced by JNK1 inhibition in OCPs. Furthermore, RANKL could induce the phosphorylation of Bcl‐2, subsequently dissociating Beclin1 from the Bcl‐2‐Beclin1 complex, which could be blocked by JNK1 inhibition. Collectively, this study revealed that JNK1 regulated osteoclastogenesis by activating Bcl‐2‐Beclin1‐autophagy signaling in addition to the classic c‐Jun/activator protein 1 pathway, which provided the first evidence for the contribution of JNK1 signaling to OCP autophagy and the autophagic mechanism underlying JNK1‐regulated osteoclastogenesis. An important osteoclastogenesis‐regulating signaling pathway (JNK1‐Bcl‐2‐Beclin1‐autophagy activation) was identified, which provides novel potential targets for the clinical therapy of metabolic bone diseases.—Ke, D., Ji, L., Wang, Y., Fu, X., Chen, J., Wang, F., Zhao, D., Xue, Y., Lan, X., Hou, J. JNK1 regulates RANKL‐induced osteoclastogenesis via activation of a novel Bcl‐2‐Beclin1‐autophagy pathway. FASEB J. 33, 11082–11095 (2019). http://www.fasebj.org

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supporting

confidence: 83%

JNK1 regulates RANKL‐induced osteoclastogenesis via activation of a novel Bcl‐2‐Beclin1‐autophagy pathway

Wang

et al. 2019

FASEB j.

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“…40,41 Prx2 gene expression was markedly upregulated in SCD mice compared with healthy controls (supplemental Figure 1C), whereas Catalase expression was similar in both mouse strains (data not shown).…”

Section: Acid As Multimodal Therapy For Sbd 2321mentioning

confidence: 89%

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Carbonare

Mattè

Valenti

et al. 2015

Blood

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Key Points• In SCD, recurrent vasoocclusive crisis suppresses osteogenic lineage and activates osteoclasts.• Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/ osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD. (Blood. 2015;126(20):2320-2328 IntroductionSickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75 000 individuals in the United States and almost 20 000 to 25 000 individuals in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharan Africa to European countries.1-3 Studies of the global burden of disease have pointed out the invalidating impact of SCD on patient quality of life.2 This requires the development of new therapeutic options to treat sickle cell-related acute and chronic complications.SCD is caused by a point mutation in the b-globin gene resulting in the synthesis of pathologic hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density, and further acceleration of HbS polymerization. [4][5][6] Pathophysiologic studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of ...

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“…SAA1, a major acute phase protein, stimulates MMP9 production for bone resorption (Paret, Schon, Szponar & Kovacs, 2010). In contrast, peroxiredoxin 2 (PRDX2), a member of the antioxidant enzyme family, is protective against oxidative damage during osteoclastogenesis (Park et al., 2015). …”

Section: Discussionmentioning

confidence: 99%

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

et al. 2018

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SummaryExosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age‐related bone loss. However, the molecular changes in serum‐derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463. Overall, 1,371 proteins were identified with an overlap of 1,160 Gene IDs among the ExoCarta proteins. Bioinformatics analysis and in vitro studies suggested that protein changes in SDEs of osteoporosis patients are not only involved in suppressing the integrin‐mediated mechanosensation and activation of osteoblastic cells, but also trigger the differentiation and resorption of osteoclasts. In contrast, the main changes in SDEs of osteopenia patients facilitated both activation of osteoclasts and formation of new bone mass, which could result in a compensatory elevation in bone remodeling. While the SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging‐associated oxidative stress. This information will be helpful in elucidating the pathophysiological functions of SDEs and aid in the development of senile osteoporosis diagnostics and therapeutics.

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Peroxiredoxin II Negatively Regulates Lipopolysaccharide-Induced Osteoclast Formation and Bone LossviaJNK and STAT3

Cited by 45 publications

References 61 publications

JNK1 regulates RANKL‐induced osteoclastogenesis via activation of a novel Bcl‐2‐Beclin1‐autophagy pathway

JNK1 regulates RANKL‐induced osteoclastogenesis via activation of a novel Bcl‐2‐Beclin1‐autophagy pathway

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

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