Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts

Zeng, Zhiyong; Zhang, Chenqing; Chen, Junmin

doi:10.1007/s00774-013-0434-0

Cited by 19 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bone diseases caused by excessive osteoclast activity such as osteoporosis and erosive arthritis can be moderated or prevented by medications that block DC‐STAMP activity. To date, miRNA (Sissons et al, ; Bernard, ; Dou et al, ; Chen et al, ) and RNA interference (Zeng et al, ) have been shown to effectively block the biological activity and gene expression of DC‐STAMP. In addition, since ITIM was present in the cytoplasmic tail of DC‐STAMP, employing ITIM‐bearing peptides to saturate and block DC‐STAMP‐interacting proteins remain an option to control DC‐STAMP function.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of DC‐STAMP at both mRNA and protein levels can be significantly and specifically inhibited by RNAi (Zeng et al, ). Of note, DC‐STAMP inhibition by RNAi consequently suppressed fusion and bone resorption of human osteoclasts, suggesting that inhibition of DC‐STAMP by RNAi is an efficient and effective method of regulating osteoclast functions.…”

Section: Regulators That Affect Dc‐stamp Expressionmentioning

confidence: 99%

“…Of note, DC‐STAMP inhibition by RNAi consequently suppressed fusion and bone resorption of human osteoclasts, suggesting that inhibition of DC‐STAMP by RNAi is an efficient and effective method of regulating osteoclast functions. Data from Zeng et al () demonstrated that the lentivirus‐mediated RNAi was capable of efficiently suppressing DC‐STAMP expression in primary human osteoclasts and inhibiting osteoclastogenesis.…”

Section: Regulators That Affect Dc‐stamp Expressionmentioning

confidence: 99%

See 2 more Smart Citations

DC-STAMP: A Key Regulator in Osteoclast Differentiation

Chiu

Ritchlin

2016

J. Cell. Physiol.

View full text Add to dashboard Cite

Osteoimmunology research is a new emerging research field that investigates the links between the bone and immune responses. Results from osteoimmunology studies suggest that bone is not only an essential component of the musculoskeletal system, but is also actively involved in immune regulation. Many important factors involved in immune regulation also participate in bone homeostasis. Bone homeostasis is achieved by a coordinated action between bone synthesizing osteoblasts and bone degrading osteoclasts. An imbalanced action between osteoblasts and osteoclasts often results in pathological bone diseases: osteoporosis is caused by an excessive osteoclast activity, whereas osteopetrosis results from an increased osteoblast activity. This review focuses on dendritic cell specific transmembrane protein (DC STAMP), an important protein currently considered as a master regulator of osteoclastogenesis. Of clinical relevance, the frequency of circulating DC STAMPþ cells is elevated during the pathogenesis of psoriatic diseases. Intriguingly, recent results suggest that DC STAMP also plays an imperative role in bone homeostasis by regulating the differentiation of both osteoclasts and osteoblasts. This article summarizes our current knowledge on DC STAMP by focusing on its interacting proteins, its regulation on osteoclastogenesis related genes, its possible involvement in immunoreceptor tyrosine based inhibitory motif (ITIM) mediated signaling cascade, and its potential of developing therapeutics for clinical applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Regulators That Affect Dc‐stamp Expressionmentioning

confidence: 99%

Section: Regulators That Affect Dc‐stamp Expressionmentioning

confidence: 99%

See 1 more Smart Citation

DC-STAMP: A Key Regulator in Osteoclast Differentiation

Chiu

Ritchlin

2016

J. Cell. Physiol.

View full text Add to dashboard Cite

show abstract

“…This protein has been shown to be expressed in dendritic cells and macrophages but predominantly in osteoclasts [34]. RNA interference studies on human osteoclasts demonstrated an essential role for osteoclastic cell–cell fusion and resorptive activity [28]. DC-STAMP-deficient mice did not develop multinucleation of osteoclasts [35].…”

Section: Introductionmentioning

confidence: 99%

Osteoclast profile of medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis

et al. 2017

View full text Add to dashboard Cite

BackgroundThe medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy [MRONJ (BP)] is characterized by non-healing exposed bone in the maxillofacial region. The pathogenesis of MRONJ (BP) is not fully understood. Giant, hypernucleated, inactive osteoclasts were found in MRONJ (BP) tissues, which indicated that accelerated cell–cell fusion might play a role. Dendritic cell-specific transmembrane protein (DC-STAMP) is associated with the cell–cell fusion of osteoclasts and precursor cells. Tartrate-resistant acid phosphatase (TRAP) is essential for osteoclastic bone resorption. The cell–cell fusion, as part of the osteoclastogenesis, and the resorptive activity can determine the morphology of osteoclasts. This study analyzed jaw bone from patients with MRONJ (BP), osteomyelitis (OM) and osteoradionecrosis (ORN) because a comparison with the osteoclast profiles of OM and ORN is essential for characterizing the osteoclast profile of MRONJ (BP).MethodsFormalin-fixed routine jaw bone specimens from 70 patients [MRONJ (BP) n = 30; OM: n = 15, ORN: n = 15, control: n = 10] were analyzed retrospectively for osteoclast quantity, morphology and the expression of TRAP and DC-STAMP. The specimens were processed for hematoxylin and eosin staining (H&E), histochemistry (TRAP) and immunohistochemistry (anti-DC-STAMP) and were analyzed via virtual microscopy.ResultsThe quantity, diameter and nuclearity of osteoclasts were significantly higher in MRONJ (BP) specimens than in OM, ORN and control specimens. Giant, hypernucleated osteoclasts were detected in MRONJ (BP) specimens only. Osteoclastic TRAP expression was lower in MRONJ (BP) and ORN specimens than in OM and control specimens. The DC-STAMP expression of osteoclasts and mononuclear cells was significantly higher in MRONJ (BP) and ORN specimens than in OM and control specimens.ConclusionsThis study indicates that the osteoclast profile of MRONJ (BP) is characterized by osteoclast inactivation and a high cell–cell fusion rate; however, the presence of giant, hypernucleated osteoclasts cannot be attributed to increased DC-STAMP-triggered cell–cell fusion alone. The incidental characterization of the osteoclast profiles of OM and ORN revealed differences that might facilitate the histopathological differentiation of these diseases from MRONJ (BP), which is essential because their therapies are somewhat different.

show abstract

“…The activities of these transcription factors consequently regulates osteoclast differentiation by upregulating the expression of osteoclast-associated genes, such www.nature.com/aps Zeng XZ et al Acta Pharmacologica Sinica npg as tartrate-resistant acid phosphatase (TRAP), cathepsin K, β3-Integrin and DC-STAMP [5] . During the differentiation of osteoclasts, the fusion of mononuclear pre-osteoclasts is a critical event during the formation of mature multinucleated osteoclasts [6] . Fusion failure can result in the severe reduction of bone-resorbing activity and an increase in bone mass, as seen in osteopetrosis [7] .…”

Section: Introductionmentioning

confidence: 99%

Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression

et al. 2015

View full text Add to dashboard Cite

Aim: Aconiti Lateralis Radix Preparata is a traditional Chinese medicine used to treat chronic arthritis and is highly effective against rheumatoid arthritis. However, the effects of aconine, a derivative of aconitum alkaloids, on osteoclasts, which can absorb bone, remain unknown. Here, we investigated the effects of aconine on osteoclast differentiation and bone resorption in vitro. Methods: The viability of mouse leukemic monocyte/macrophage cell line RaW264.7 was measured using CCK-8 assays. osteoclast differentiation was induced by incubation of RaW264.7 cells in the presence of RanKL, and assessed with TRaP staining assay. Bone resorption was examined with bone resorption pits assay. The expression of relevant genes and proteins was analyzed using RT-PCR and Western blots. The activation of NF-κB and nuclear factor of activated T-cells (NFAT) was examined using stable NF-κB and NFATc1 luciferase reporter gene systems, RT-PCR and Western blot analysis. Results: Aconine (0.125, 0.25 μmol/L) did not affect the viability of RAW264.7 cells, but dose-dependently inhibited RANKL-induced osteoclast formation and bone resorptive activity. Furthermore, aconine dose-dependently inhibited the RanKL-induced activation of NF-κB and NFATc1 in RAW264.7 cells, and subsequently reduced the expression of osteoclast-specific genes (c-Src, β3-Integrin, cathepsin K and MMP-9) and the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which played an important role in cell-cell fusion. Conclusion: These findings suggest that aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing the activation of NF-κB and NFATc1 and the expression of the cell-cell fusion molecule DC-STAMP.

show abstract

Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts

Cited by 19 publications

References 20 publications

DC-STAMP: A Key Regulator in Osteoclast Differentiation

DC-STAMP: A Key Regulator in Osteoclast Differentiation

Osteoclast profile of medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis

Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression

Contact Info

Product

Resources

About