Dual Effect of Cyanidin on RANKL‐Induced Differentiation and Fusion of Osteoclasts

Dou, Ce; Li, Jianmei; Kang, Fei; Cao, Zhen; Yang, Xiaochao; Jiang, Hong; Yang, Bo; Xiang, Junyu; Xu, Jianzhong; Dong, Shiwu

doi:10.1002/jcp.24916

Cited by 48 publications

(35 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tetraspanins, such as CD9 and CD81, are characteristic markers and membranous components of exosomes [17][18][19][20][21]. CD9 is a transmembrane protein associated with angiogenesis via cell adhesion, migration, and signal transduction, and it is involved in cell fusion processes linked to fertilization, osteoclastogenesis, and myogenesis [22][23][24][25][26][27][28][29][30]. Eggs and dendritic cells from CD9-deficient mice release reduced levels of exosomes [31,32].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Furuta

Miyaki

Ishitobi

et al. 2016

Stem Cells Translational Medicine

371

362

View full text Add to dashboard Cite

Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. Although the production of regulatory cytokines by MSC transplantation is a critical modulator of tissue regeneration, we focused on exosomes, which are extracellular vesicles that contain proteins and nucleic acids, as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we used radiologic imaging, histological examination, and immunohistochemical analysis to evaluate the role of exosomes isolated from MSC-conditioned medium (CM) in the healing process in a femur fracture model of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. We found that the bone union rate in CD9 2/2 mice was significantly lower than wild-type mice because of the retardation of callus formation. The retardation of fracture healing in CD9 2/2 mice was rescued by the injection of exosomes, but this was not the case after the injection of exosomes-free conditioned medium (CM-Exo). The levels of the bone repairrelated cytokines, monocyte chemotactic protein-1 (MCP-1), MCP-3, and stromal cell-derived factor-1 in exosomes were low compared with levels in CM and CM-Exo, suggesting that bone repair may be in part mediated by other exosome components, such as microRNAs. These results suggest that exosomes in CM facilitate the acceleration of fracture healing, and we conclude that exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1620-1630 SIGNIFICANCEThis work focuses on exosomes, which are extracellular vesicles, as a novel additional modulator of cell-to-cell communication. This study evaluated the role of exosomes isolated from mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) in the fracture-healing process of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. Retardation of fracture healing in CD9 2/2 mice was rescued by the injection of MSC exosomes, but this was not the case after the injection of exosome-free CM. This study finds that MSC exosomes are a novel factor of MSC paracrine signaling, with an important role in the tissue repair process.

show abstract

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Furuta

Miyaki

Ishitobi

et al. 2016

Stem Cells Translational Medicine

371

362

View full text Add to dashboard Cite

show abstract

“…The second stage is bone substance destruction, which is accomplished by osteoclasts. Osteoclasts are differentiated from monocyte/macrophage lineage cells8. Osteoclast activation is the most important process in bone destruction91011.…”

mentioning

confidence: 99%

TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation

Jiang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.

show abstract

“…Bleach solution was added to remove cells. Detailed analysis of pit formation area was described previously (9).…”

Section: Methodsmentioning

confidence: 99%

HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis

Dou

Ding

et al. 2016

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

The bone-resorbing osteoclast (OC) is essential for bone homeostasis, yet deregulation of OCs contributes to diseases such as osteoporosis, osteopetrosis, and rheumatoid arthritis. Here we show that histone deacetylase 2 (HDAC2) is a key positive regulator during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Bone marrow macrophages (BMMs) showed increased HDAC2 expression during osteoclastogenesis. HDAC2 overexpression enhanced, whereas HDAC2 deletion suppressed osteoclastogenesis and bone resorption using lentivirus infection. Mechanistically, upon RANKL activation, HDAC2 activated Akt; Akt directly phosphorylates and abrogates Forkhead box protein O1 (FoxO1), which is a negative regulator during osteoclastogenesis through reducing reactive oxygen species. HDAC2 deletion in BMMs resulted in decreased Akt activation and increased FoxO1 activity during osteoclastogenesis. In conclusion, HDAC2 activates Akt thus suppresses FoxO1 transcription results in enhanced osteoclastogenesis. Our data imply the potential value of HDAC2 as a new target in regulating osteoclast differentiation and function.

show abstract

Dual Effect of Cyanidin on RANKL‐Induced Differentiation and Fusion of Osteoclasts

Cited by 48 publications

References 61 publications

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation

HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis

Contact Info

Product

Resources

About