Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model

Abstract Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients’ quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

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OA-4 Inhibits Osteoclast Formation and Bone Resorption via Suppressing RANKL Induced P38 Signaling Pathway

Current Medicinal Chemistry ◽

10.2174/09298673113209990190 ◽

2014 ◽

Vol 21 (5) ◽

pp. 641-649 ◽

Cited By ~ 12

Author(s):

B. Tian ◽

A. Qin ◽

Z.Y. Shao ◽

T. Jiang ◽

Z.J. Zhai ◽

...

Keyword(s):

Bone Resorption ◽

Signaling Pathway ◽

Osteoclast Formation

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Biological Effects of β-Glucans on Osteoclastogenesis

Molecules ◽

10.3390/molecules26071982 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1982

Author(s):

Wataru Ariyoshi ◽

Shiika Hara ◽

Ayaka Koga ◽

Yoshie Nagai-Yoshioka ◽

Ryota Yamasaki

Keyword(s):

Bone Resorption ◽

Bone Marrow Cells ◽

Biological Effects ◽

Osteoclast Differentiation ◽

Treatment Strategies ◽

Alcaligenes Faecalis ◽

Osteoclast Formation ◽

Osteoclast Precursors

Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker’s yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo. However, zymosan derived from S. cerevisiae stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases.

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Using machine learning to automate image segmentation for analysis of in vitro osteoclast formation and bone resorption

Bone Reports ◽

10.1016/j.bonr.2021.100865 ◽

2021 ◽

Vol 14 ◽

pp. 100865

Author(s):

B.K. Davies ◽

Andrew Hibbert ◽

Mark Hopkinson ◽

Gill Holdsworth ◽

Isabel Orriss

Keyword(s):

Machine Learning ◽

Image Segmentation ◽

Bone Resorption ◽

Osteoclast Formation

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Paclitaxel inhibits osteoclast formation and bone resorption via influencing mitotic cell cycle arrest and RANKL-induced activation of NF-κB and ERK

Journal of Cellular Biochemistry ◽

10.1002/jcb.23423 ◽

2012 ◽

Vol 113 (3) ◽

pp. 946-955 ◽

Cited By ~ 14

Author(s):

Estabelle S. M. Ang ◽

Nathan J. Pavlos ◽

Shek Man Chim ◽

Hao Tian Feng ◽

Robin M. Scaife ◽

...

Keyword(s):

Cell Cycle ◽

Bone Resorption ◽

Cell Cycle Arrest ◽

Mitotic Cell ◽

Osteoclast Formation ◽

Mitotic Cell Cycle ◽

Cycle Arrest

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Inhibitory effect of ipriflavone on osteoclast-mediated bone resorption and new osteoclast formation in long-term cultures of mouse unfractionated bone cells

Calcified Tissue International ◽

10.1007/bf01321839 ◽

1993 ◽

Vol 53 (3) ◽

pp. 206-209 ◽

Cited By ~ 18

Author(s):

Kohei Notoya ◽

Keiji Yoshida ◽

Shigehisa Taketomi ◽

Iwao Yamazaki ◽

Masayoshi Kumegawa

Keyword(s):

Bone Resorption ◽

Bone Cells ◽

Inhibitory Effect ◽

Osteoclast Formation

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R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

10.1101/332551 ◽

2018 ◽

Author(s):

Maayan Barnea ◽

Merle Stein ◽

Sabina Winograd-Katz ◽

Moran Shalev ◽

Esther Arman ◽

...

Keyword(s):

Bone Resorption ◽

Mouse Model ◽

Autosomal Recessive ◽

Molecular Mechanisms ◽

Precursor Cell ◽

Unique Combination ◽

Sorting Nexin ◽

Autosomal Recessive Osteopetrosis

SummaryThe molecular mechanisms that regulate fusion of monocytes into functional osteoclasts are virtually unknown. We describe a knock-in mouse model for the R51Q mutation in sorting nexin 10 (SNX10) that exhibits osteopetrosis and related symptoms of patients of autosomal recessive osteopetrosis linked to this mutation. Osteopetrosis arises in homozygous R51Q SNX10 mice due to a unique combination of reduced numbers of osteoclasts that are non-functional. Fusion of mutant monocytes is deregulated and occurs rapidly and continuously to form giant, non-functional osteoclasts. Mutant osteoclasts mature quickly and survive poorly in vitro, possibly accounting for their scarcity in vivo. These cells also exhibit impaired ruffled borders, which are required for bone resorption, providing an additional basis for the osteopetrotic phenotype. More broadly, we propose that the maximal size of osteoclasts is actively determined by a genetically-regulated, cell-autonomous mechanism that limits precursor cell fusion, and for which SNX10 is required.

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Pyridone 6, A Pan-Janus-Activated Kinase Inhibitor, Suppresses Osteoclast Formation and Bone Resorption through Down-Regulation of Receptor Activator of Nuclear Factor-κB (NF-κB) Ligand (RANKL)-Induced c-Fos and Nuclear Factor of Activated T Cells (NFAT) c1 Expression

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.32.45 ◽

2009 ◽

Vol 32 (1) ◽

pp. 45-50 ◽

Cited By ~ 10

Author(s):

Han Bok Kwak ◽

Hun Soo Kim ◽

Myeung Su Lee ◽

Kwang-Jin Kim ◽

Eun-Yong Choi ◽

...

Keyword(s):

T Cells ◽

Bone Resorption ◽

Kinase Inhibitor ◽

Nuclear Factor Κb ◽

Osteoclast Formation ◽

Nuclear Factor ◽

Down Regulation ◽

Activated T Cells ◽

Receptor Activator

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Inhibition of intravacuolar acidification by antisense RNA decreases osteoclast differentiation and bone resorption in vitro

Journal of Cell Science ◽

10.1242/jcs.112.21.3657 ◽

1999 ◽

Vol 112 (21) ◽

pp. 3657-3666 ◽

Cited By ~ 1

Author(s):

T. Laitala-Leinonen ◽

C. Lowik ◽

S. Papapoulos ◽

H.K. Vaananen

Keyword(s):

Bone Marrow ◽

Bone Resorption ◽

Antisense Rna ◽

Osteoclast Differentiation ◽

Osteoclast Formation ◽

Gm Csf ◽

Monocytes And Macrophages ◽

Marrow Cultures ◽

Rat Bone

The role of proton transport and production in osteoclast differentiation was studied in vitro by inhibiting the transcription/translation of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) by antisense RNA molecules. Antisense RNAs targeted against CA II, or the 16 kDa or 60 kDa subunit of V-ATPase were used to block the expression of the specific proteins. A significant decrease in bone resorption rate and TRAP-positive osteoclast number was seen in rat bone marrow cultures and fetal mouse metacarpal cultures after antisense treatment. Intravacuolar acidification in rat bone marrow cells was also significantly decreased after antisense treatment. The CA II antisense RNA increased the number of TRAP-positive mononuclear cells, suggesting inhibition of osteoclast precursor fusion. Antisense molecules decreased the number of monocytes and macrophages, but increased the number of granulocytes in marrow cultures. GM-CSF, IL-3 and IL-6 were used to stimulate haematopoietic stem cell differentiation. The 16 kDa V-ATPase antisense RNA abolished the stimulatory effect of GM-CSF, IL-3 and IL-6 on TRAP-positive osteoclast formation, but did not affect the formation of monocytes and macrophages after IL-3 treatment, or the formation of granulocytes after IL-6 treatment. These results suggest that CA II and V-ATPase are needed, not only for the actual resorption, but also for osteoclast formation in vitro.

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