Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation

Yi, Sun‐Ju; Lee, Hye-Rim; Lee, Jisu; Lee, Kyubin; Kim, Junil; Kim, Yeojin; Park, Jae-Il; Kim, Kyung-Hwan

doi:10.3390/ijms20133147

Cited by 49 publications

(39 citation statements)

References 129 publications

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“…Moreover, osteoblasts and osteoclasts play crucial roles in bone remodeling [29]. To maintain skeletal integrity, osteoclast and osteoblast activity must be precisely coordinated [30]. Osteoblasts are derived from bone marrow mesenchymal stem cells and actively promote subsequent bone formation [30].…”

Section: Discussionmentioning

confidence: 99%

“…To maintain skeletal integrity, osteoclast and osteoblast activity must be precisely coordinated [30]. Osteoblasts are derived from bone marrow mesenchymal stem cells and actively promote subsequent bone formation [30]. Osteoclasts are multinucleated cells derived from macrophages and monocytes of the hematopoietic stem cell lineage [31].…”

Section: Discussionmentioning

confidence: 99%

“…After 24 h of incubation in a serum-free medium, cells were present in 1 ng/mL recombinant IL-16 protein. At 15,30,60, and 120 min, total protein extraction was performed using a protein extraction buffer (Sigma-Aldrich, USA) containing cOmplete protease inhibitor cocktail (Sigma-Aldrich, USA) and phosphatase inhibitor cocktails 2 and 3 (Sigma-Aldrich, USA). Protein samples were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to a polyvinylidene fluoride (PVDF) membrane (Merck Millipore, Darmstadt, Germany).…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

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Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Chang

Hsiao

et al. 2020

IJMS

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Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.Int. J. Mol. Sci. 2020, 21, 2904 2 of 15 of differentiation 4 (CD4 + ) lymphocytes, monocytes, and eosinophils [11,12]. IL-16 is synthesized as a precursor protein (pro-IL-16) of approximately 68 kDa. Pro-IL-16 is cleaved by activated caspase-3 and then IL-16 generation [13]. CD4 serves as a signaling transducing receptor for IL-16 signaling. Increased intracytoplasmic calcium and inositol trisphosphate can be initiated when IL-16 interacts with CD4 receptors, and this subsequently activates stress-activated protein kinases (SAPKs) p46 and p54. Stimulation with IL-16 also activates members of the mitogen-activated protein kinase (MAPK) family, namely c-Jun N-terminal kinase (JNK) and p38 but does not activate extracellular signal-regulated kinase (ERK)-1 or ERK-2 [14]. IL-16 can activate monocytes and stimulate the secretion of inflammatory cytokines, chiefly tumor necrosis factor (TNF)-α, IL-1β, 15,16]. Currently, these cytokines are believed to promote the development of septic arthritis [17][18][19].PJI can result from Gram-positive (GP) or Gram-negative (GN) bacterial infections. Our previous retrospective study revealed that GN infections were associated with an increased risk of aseptic loosening as compared with GP infections [20]. The cell walls of GP bacteria contain lipoteichoic acid (LTA) components, whereas those of GN bacteria contain components of lipopolysaccharide (LPS). In studies of mice receiving intrafemoral injections of LPS or LTA, LPS reduced both the number of trabeculae and bone mineral density, whereas LTA did not have this effect [20]. In addition, disruption of the bal...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Chang

Hsiao

et al. 2020

IJMS

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“…The epigenetic modification mechanisms mainly include DNA methylation, histone tail modification, and non-coding RNA regulation, all of which modulate gene expression without changing the DNA sequence [20][21][22]. DNA hypermethylation is generally associated with gene silencing [23,24].…”

Section: Introductionmentioning

confidence: 99%

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

Sun

Dong

et al. 2020

Toxins

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Mastitis is usually caused by a variety of pathogenic bacteria that include both Gram-positive and Gram-negative bacteria. Lipopolysaccharide (LPS) is the pathogen-associated molecular pattern (PAMP) of Gram-negative bacteria, and peptidoglycan (PGN) and lipoteichoic acid (LTA) are those of Gram-positive bacteria. The effects of LPS, PGN and/or LTA on inflammatory response and lactation in bovine mammary epithelial cells (BMECs) are well studied, but the epigenetic mechanisms of their effects received less attention. Furthermore, since the three PAMPs are often simultaneously present in the udder of cows with mastitis, it has implications in practice to study their additive effects. The results show that co-stimulation of bovine mammary epithelial cells with PGN, LTA, and LPS induced a higher number of differentially expressed genes (DEGs) and greater expressions of inflammatory factors including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand (CXCL)1, and CXCL6. In addition, co-stimulation further increased DNA hypomethylation compared with sole LPS stimulation. Co-stimulation greatly decreased casein expression but did not further decrease histone acetylation levels and affect the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC), compared with sole LPS stimulation. Collectively, this study demonstrated that PGN, LTA, and LPS had an additive effect on inducing transcriptome changes and inflammatory responses in BMECs, probably through inducing a greater decrease in DNA methylation. Co-stimulation with PGN, LTA, and LPS decreased casein expression to a greater degree, but it might not be linked to histone acetylation and HAT and HDAC activity.

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“…Osteoclasts are multinucleated giant cells that are responsible for bone degradation. They are formed by the fusion of mononuclear precursors of the hematopoietic stem cell lineage [5,6]. Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL) are two essential ligands for osteoclast differentiation.…”

Section: Introductionmentioning

confidence: 99%

Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression

Lee

et al. 2020

IJMS

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Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.

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Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation

Cited by 49 publications

References 129 publications

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression

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