The Adaptor Protein p62 Is Involved in RANKL-induced Autophagy and Osteoclastogenesis

Li, Ruifang; Chen, Gang; Ren, Jian‐Gang; Zhang, Wei; Wu, Zehua; Liu, Bing; Zhao, Yi

doi:10.1369/0022155414551367

Cited by 67 publications

(54 citation statements)

References 41 publications

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“…p62 is a multifunctional protein containing a number of protein‐protein interaction motifs that are involved in protein aggregation and degradation . It has been reported that autophagy dysfunction or defects will cause p62 upregulation .…”

Section: Discussionmentioning

confidence: 99%

“…p62 is a multifunctional protein containing a number of protein-protein interaction motifs that are involved in protein aggregation and degradation. 24 It has been reported that autophagy dysfunction or defects will cause p62 upregulation. 25 Based on evidence of p62 partial restoration, recent research proved that chloroquine is an autophagy inhibitor and further increases LC3II/LC3I expression in rats.…”

Section: Discussionmentioning

confidence: 99%

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β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

Huang

Deng

et al. 2015

Clin Exp Pharma Physio

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In this study, we investigated Beclin-1, light chain (LC)3B, and p62 expression in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats after β-asarone and levodopa (l-dopa) co-administration. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create the models, except in sham-operated rats. Rats were divided into eight groups: sham-operated group; 6-OHDA model group; madopar group (75 mg/kg, per os (p.o.)); l-dopa group (60 mg/kg, p.o.); β-asarone group (15 mg/kg, p.o.); β-asarone + l-dopa co-administered group (15 mg/kg + 60 mg/kg, p.o.); 3-methyladenine group (500 nmol, intraperitoneal injection); and rapamycin group (1 mg/kg, intraperitoneal injection). Then, Beclin-1, LC3B, and p62 expression in the mesencephalon were detected. The mesencephalon was also observed by transmission electron microscope. The results showed that Beclin-1 and LC3B expression decreased and that p62 expression increased significantly in the madopar, l-dopa, β-asarone, and co-administered groups when compared with the 6-OHDA model. Beclin-1 and LC3B expression in the β-asarone and co-administered groups were less than in the madopar or l-dopa groups, whereas p62 expression in the β-asarone and co-administered groups was higher than in the madopar or l-dopa groups. In addition, a significant decrease in autophagosome was exhibited in the β-asarone and co-administered groups when compared with the 6-OHDA group. Our findings indicate that Beclin-1 and LC3B expression decreased, whereas p62 expression increased after co-administration treatment. In sum, all data suggest that the co-administration of β-asarone and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

Huang

Deng

et al. 2015

Clin Exp Pharma Physio

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“…[62][63][64] Studies indicate that autophagy also plays an important role in bone resorption by osteoclasts. 65 It has been reported that proteins involved in the autophagic pathway are important in the regulation of osteoclastogenesis, 66,67 indicating that this process participates both in bone formation and resorption. There is evidence that resorptive activity is decreased when bafilomycin, an autophagy inhibitor, is added to the culture of osteoclasts.…”

Section: Role Of Autophagy In Bone Biologymentioning

confidence: 99%

Osteoporosis and autophagy: What is the relationship?

Florencio‐Silva

Sasso

Simões

et al. 2017

Rev. Assoc. Med. Bras.

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Autophagy is a survival pathway wherein non-functional proteins and organelles are degraded in lysosomes for recycling and energy production. Therefore, autophagy is fundamental for the maintenance of cell viability, acting as a quality control process that prevents the accumulation of unnecessary structures and oxidative stress. Increasing evidence has shown that autophagy dysfunction is related to several pathologies including neurodegenerative diseases and cancer. Moreover, recent studies have shown that autophagy plays an important role for the maintenance of bone homeostasis. For instance, in vitro and animal and human studies indicate that autophagy dysfunction in bone cells is associated with the onset of bone diseases such as osteoporosis. This review had the purpose of discussing the issue to confirm whether a relationship between autophagy dysfunction and osteoporosis exits.

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“…The involvement of autophagy in the proliferation and differentiation of osteoclasts, as well as the activity of bone absorption, has been proven (17)(18)(19). Autophagy was strongly activated in response to RANKL (20,21). Xiu et al (22) also reported the key role of RANKL in the formation of autolysosomes, subsequently promoting osteoclastogenesis.…”

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confidence: 99%

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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The Adaptor Protein p62 Is Involved in RANKL-induced Autophagy and Osteoclastogenesis

Cited by 67 publications

References 41 publications

β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

Osteoporosis and autophagy: What is the relationship?

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

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