Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

Oh, Se Jeong; Gu, Dong Ryun; Jin, Su Hyun; Park, Keun Ha; Lee, Seoung Hoon

doi:10.1016/j.bbrc.2016.05.055

Cited by 23 publications

(21 citation statements)

References 32 publications

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“…Osteoclastic differentiation, acid secretion and skeletal rearrangement are continuous physiological processes that ensure the bone resorptive capacity of mature osteoclasts. In addition, malate dehydrogenase (MDH) regulates the malate-aspartate shuttle between the cytoplasm and mitochondria relying on the coenzyme nicotinamide adenine dinucleotide (NAD + /NADH), thereby regulating cellular energy metabolism and interfering with osteoclast differentiation and function ( 47 ). MDH1 located in the cytoplasm catalyzes the reduction of oxaloacetate to malate, which is further converted to oxaloacetate by MDH2 in mitochondrial matrix.…”

Section: Phenotypic Changes In Osteoclasts During the Development Of Osteoporosis Based On Energy Metabolismmentioning

confidence: 99%

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Lin

Zhu

2021

Front. Endocrinol.

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In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.

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Section: Phenotypic Changes In Osteoclasts During the Development Of Osteoporosis Based On Energy Metabolismmentioning

confidence: 99%

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Lin

Zhu

2021

Front. Endocrinol.

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“…Total RNA (1 μg), prepared from BMMs using the TRIzol reagent, was reverse transcribed to cDNA with random primers using the SuperScript II RT-PCR System (Invitrogen) according to the manufacturer’s instructions, followed by PCR for Ablim1 . Real-time PCR for osteoclast marker genes was performed using the VeriQuest SYBR Green qPCR Master Mix (Thermo Scientific, Waltham, MA, USA) and the StepOnePlus Real-Time PCR System (Applied Biosystems, Waltham, MA, USA) as previously described ( 29 , 30 ). The relative expression levels were normalized to the level of Gapdh mRNA.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were lysed, and proteins were extracted using M-PER Mammalian Protein Extraction Reagent (Thermo Scientific), supplemented with protease inhibitor cocktail (Roche, Mannheim, Germany) and phosphatase inhibitor (Thermo Scientific). Extracted proteins (30–50 μg) were subjected to SDS-PAGE and then electroblotted onto polyvinylidene difluoride membranes (Hybond-P, GE-Healthcare Life Science, Pittsburgh, PA, USA) as previously described ( 29 , 30 ). After the application of primary and secondary antibodies, signals were visualized using the Enhanced Chemiluminescence detection system (Thermo Scientific) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

Jin

Kim

et al. 2018

BMB Rep.

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Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

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“…In mammalian cells, AMPK coordinates the regulatory metabolism of energy changes, autophagy and cell growth (Figure 2) (Mihaylova and Shaw, 2011). As mentioned above, activated AMPK suppresses the differentiation and function of osteoclasts induced by RANKL through a reduction of c-Fos and NFATc1 expression, as well as specific approaches (Jeyabalan et al, 2012;Oh et al, 2016). Recently, extensive studies have reported that energy plays a critical role in bone metabolism, whereas the differentiation and function of osteoclasts are regulated by autophagy.…”

Section: Activated Ampk Negatively Regulates Osteoclast Differentiatimentioning

confidence: 97%

AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs

Tong

Ganta

Liu

2020

Biology of the Cell

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Osteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast‐mediated bone formation. Studies have demonstrated that AMP‐activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK‐mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa‐B ligand‐induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone‐related diseases, as well as function as a biomarker for bone homoeostasis.

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Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

Cited by 23 publications

References 32 publications

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs

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