Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling

Zhang, Wei; Hou, Weiduo; Chen, Mo; Chen, Erman; Xue, Deting; Ye, Chenyi; Li, Weixu; Pan, Zhijun

doi:10.3389/fcell.2020.576104

Cited by 14 publications

(14 citation statements)

References 51 publications

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“…Cell Counting Kit-8 (CCK-8) reagents were purchased from Dojindo (Kumamoto, Japan). According to our previous report [ 14 ], a siRNA sequence targeted to Parkin (sense strand: 5′-CCUUCUGCCGGGAAUGUAATT-3′, antisense strand: 5′-UUACAUUCCCGGCAGAAGGTT-3′) and a negative control siRNA (sense strand: 5′-UUCUCCGAACGUGUCACGUTT-3′ and antisense strand: 5′-ACGUGACACGUUCGGAGAATT-3′) were purchased from GenePharma Inc. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

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Parkin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss

Hou

Chen

et al. 2022

Biomolecules

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Osteoporosis and osteoporotic fractures comprise a substantial health and socioeconomic burden. The leading cause of osteoporosis is an imbalance in bone formation and bone resorption caused by hyperactive osteoclasts. Therefore, a new strategy to suppress osteoclastogenesis is needed. Parkin is likely closely associated with bone metabolism, although its role in osteoclastogenesis is unclear. In this study, the Parkin protein inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation in vitro. Moreover, depletion of Parkin enhanced RANKL-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation. Reactive oxygen species (ROS) activity was suppressed, while autophagy was upregulated with the presence of the Parkin protein. ROS activity was upregulated and autophagy was decreased due to Parkin knockdown. In addition, intravenous administration of Parkin rescued ovariectomy-induced bone loss and reduced osteoclastogenesis in vivo. Collectively, Parkin has therapeutic potential for diseases associated with overactive osteoclasts.

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Section: Methodsmentioning

confidence: 99%

“…In adipose-derived mesenchymal stem cells, osteogenic differentiation was reportedly reduced by downregulation of Parkin [ 8 ]. Moreover, Parkin has been shown to accelerate stem cell osteogenesis [ 14 ]. Osteoclasts are crucial in the development and progress of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Parkin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss

Hou

Chen

et al. 2022

Biomolecules

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“…Parkin can be recruited to mitochondria and mediates mitochondrial autophagy, which is related to the pathogenesis of Parkinson's disease [ 101 ]. It reduces ROS levels and inhibits apoptosis in osteoarthritic chondrocytes by promoting mitophagy to eliminate damaged/depolarized mitochondria [ 102 ] What is more, Parkin promotes osteoblast differentiation of BMSCs by enhancing autophagy and β -catenin signaling pathway [ 103 ]. NIPA2 is a selective Mg2+ transporter and helps maintain Mg2+ influx.…”

Section: Effect Of E3 Ubiquitin Ligases In Skeletal Cell Fate and Pat...mentioning

confidence: 99%

E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration

Zeng

Xiong

Lin

et al. 2022

Stem Cells International

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The ubiquitination-proteasome system (UPS) is crucial in regulating a variety of cellular processes including proliferation, differentiation, and survival. Ubiquitin protein ligase E3 is the most critical molecule in the UPS system. Dysregulation of the UPS system is associated with many conditions. Over the past few decades, there have been an increasing number of studies focusing on the UPS system and how it affects bone metabolism. Multiple E3 ubiquitin ligases have been found to mediate osteogenesis or osteolysis through a variety of pathways. In this review, we describe the mechanisms of UPS, especially E3 ubiquitin ligases on bone metabolism. To date, many E3 ubiquitin ligases have been found to regulate osteogenesis or osteoclast differentiation. We review the classification of these E3 enzymes and the mechanisms that influence upstream and downstream molecules and transduction pathways. Finally, this paper reviews the discovery of the relevant UPS inhibitors, drug molecules, and noncoding RNAs so far and prospects the future research and treatment.

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“…Based on previous studies, NF-κB signaling promotes β-catenin ubiquitination and degradation through the induction of the Smad ubiquitin regulatory factor (Smurf) 1 and Smurf2 (Chang et al, 2013), and AKT signaling activates β-catenin through the phosphorylation and inactivation of glycogen synthase kinase-3β (GSK-3β) (Zheng et al, 2018). Hence, NF-κB and AKT may synergistically regulate the expression and activation of βcatenin, which has been widely reported to play a vital role in improving osteogenesis and angiogenesis (Houschyar et al, 2018;Martowicz et al, 2019;Zhang et al, 2020). Therefore, ADM2 might have a stimulatory effect on bone regeneration by improving the osteogenic differentiation and the pro-angiogenic potential of BMSCs through the accumulation and activation of β -catenin.…”

Section: Introductionmentioning

confidence: 99%

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

Wang

Kong

et al. 2021

Front. Cell Dev. Biol.

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Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. In the present study, we found that osteogenic induction enhanced the pro-angiogenic potential of BMSCs, and ADM2 treatment further improved the osteogenic differentiation and pro-angiogenic potential of BMSCs. Moreover, the accumulation and activation of β-catenin, which is mediated by the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the activation of protein kinase B (AKT), have been shown to contribute to the effects of ADM2 on BMSCs. In vivo, ADM2 accelerated vessel expansion and bone regeneration, as revealed by improved radiological and histological manifestations and the biomechanical parameters in a rat DO model. Based on the present results, we concluded that ADM2 accelerates bone regeneration during DO by enhancing the osteogenic differentiation and pro-angiogenic potential of BMSCs, partly through the NF-κB/β-catenin and AKT/β-catenin pathways. Moreover, these findings imply that BMSC-mediated coupling of osteogenesis and angiogenesis may be a promising therapeutic strategy for DO patients.

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Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling

Cited by 14 publications

References 51 publications

Parkin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss

Parkin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss

E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

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