Adenoviral down-regulation of osteopontin inhibits human osteoclast differentiation in vitro

2004 ◽  
Vol 93 (5) ◽  
pp. 896-903 ◽  
Author(s):  
Cathy J. Aitken ◽  
Jason M. Hodge ◽  
Geoffrey C. Nicholson
Keyword(s):  
Osteoclast Differentiation ◽  
Down Regulation ◽  
Human Osteoclast

Thalidomide Derivative CC-4047 Inhibits Osteoclast Formation by down Regulation of PU.1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 629-629 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Gulsum Anderson ◽  
Noriyoshi Kurihara ◽  
Tadashi Honjo ◽  
Judith Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Early Event ◽  
Down Regulation ◽  
Bone Marrow Cultures

Abstract CC-4047 (Actimid) is an immunomodulatory analog of thalidomide that has stronger anti-myeloma and anti-angiogenic activity than thalidomide, but its effects on human osteoclast lineage are unknown. Early osteoclast progenitors are of hematopoietic origin and progressively differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFκ-B ligand/M-CSF stimulated culture system of bone marrow cells. Three weeks of treatment of primary bone marrow cultures with 100 μM CC-4047 decreased osteoclast formation accompanied by complete inhibition of bone resorption. Interestingly, osteoclast formation was also inhibited when cultures were treated with CC-4047 only for the first week (90% inhibition). In contrast, inhibitory effect was greatly diminished when the drug was given for only the last week (25% inhibition), indicating that inhibition of osteoclast formation is an early event. The inhibitory effect of CC-4047 on osteoclastogenesis was not induced by cell death, but by a shift of lineage commitment to granulocyte-CFU at the expense of GM-CFU that are osteoclast progenitors. Further studies revealed that this shift is mediated through down regulation of the transcription factor PU.1, which is critical for early osteoclast formation. In contrast to CC-4047, thalidomide was a significantly less potent inhibitor of osteoclast formation and bone resorption. These results provide the first evidence that CC-4047 blocks osteoclast differentiation at the early phase of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug targeting both the tumor and osteoclastic activity in patients with multiple myeloma and potentially other diseases associated with the development of osteolytic lesions.

scholarly journals Down-regulation of Irf8 by Lyz2-cre/loxP accelerates osteoclast differentiation in vitro

2016 ◽  
Vol 69 (3) ◽  
pp. 443-450 ◽  
Author(s):  
Emi Saito ◽  
Dai Suzuki ◽  
Daisuke Kurotaki ◽  
Ayako Mochizuki ◽  
Yoko Manome ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Down Regulation

scholarly journals A Combination of Osteoclast Differentiation Factor and Macrophage-Colony Stimulating Factor Is Sufficient for both Human and Mouse Osteoclast Formation in Vitro

Endocrinology ◽  
1998 ◽  
Vol 139 (10) ◽  
pp. 4424-4427 ◽  
Author(s):  
Julian M. W. Quinn ◽  
Jan Elliott ◽  
Matthew T. Gillespie ◽  
T. John Martin
Keyword(s):  
Bone Resorption ◽  
Stromal Cells ◽  
Osteoclast Differentiation ◽  
Colony Stimulating Factor ◽  
Human Osteoclast ◽  
Osteoclast Differentiation Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Both human and murine osteoclasts can be derived in vitro from hematopoietic cells or monocytes that are cocultured with osteoblasts or marrow-derived stromal cells. The osteoclastogenic stimulus provided by murine osteoblasts and marrow-derived stromal cells is now known to be mediated by osteoclast differentiation factor (ODF), a membrane-bound tumor necrosis factor-related ligand. This study demonstrates that mouse spleen cells and monocytes form osteoclasts when cultured in the presence of macrophage-colony stimulating factor (M-CSF) and a soluble form of murine ODF (sODF). Numerous multinucleated osteoclasts expressing tartrate resistant acid phosphatase (TRAP) and calcitonin receptor (CTR) formed within 7 days of culture and engaged in extensive lacunar bone resorption. Osteoclast number and bone resorption area was dependent on sODF concentration. Long-term cultured human monocytes also formed bone resorbing osteoclasts in response to co-stimulation by sODF and M-CSF, although this required more than 11 days in culture. This human osteoclast differentiation was strongly inhibited by granulocyte-macrophage colony stimulating factor. This study further characterises murine osteoclast differentiation caused by sODF and M-CSF co-stimulation in vitro, and shows that the same co-stimulation causes human osteoclast differentiation to occur. We propose that this methodology can be employed to investigate the direct effects of cytokines and other factors on human osteoclast differentiation.

scholarly journals Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chiara Cugno ◽  
Dhanya Kizhakayil ◽  
Rita Calzone ◽  
Shaikh Mizanoor Rahman ◽  
Ganesh V. Halade ◽  
...  
Keyword(s):  
Bone Loss ◽  
Fish Oil ◽  
Inflammatory Cytokines ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Omega 3 ◽  
Down Regulation ◽  
Insulin Sensitizer ◽  
Ppar Γ

AbstractRosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.

scholarly journals PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2202-2212 ◽  
Author(s):  
Tomohiro Hikata ◽  
Hironari Takaishi ◽  
Jiro Takito ◽  
Akihiro Hakozaki ◽  
Mitsuru Furukawa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transgenic Mice ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Raw264.7 Cells ◽  
Cytokine Signaling ◽  
Tartrate Resistant Acid Phosphatase ◽  
Down Regulation ◽  
Osteoclast Precursors

Abstract Cytokine signaling via various transcription factors regulates receptor activator of nuclear factor (NF)–κB ligand (RANKL)–mediated osteoclast differentiation from monocyte/macrophage lineage cells involved in propagation and resolution of inflammatory bone destruction. Protein inhibitor of activated STAT3 (PIAS3) was initially identified as a molecule that inhibits DNA binding of STAT3 and regulates many transcription factors through distinct mechanisms. To analyze PIAS3 function in osteoclasts in vivo, we have generated transgenic mice in which PIAS3 is specifically expressed in the osteoclast lineage using the tartrate-resistant acid phosphatase (TRAP) gene promoter. PIAS3 transgenic mice showed an osteopetrotic phenotype due to impairment of osteoclast differentiation. Overexpression of PIAS3 in RAW264.7 cells suppressed RANKL-induced osteoclastogenesis by inhibiting the expression of c-Fos and NFATc1. Interestingly, PIAS3 inhibits the transcriptional activity of microphthalmiaassociated transcription factor (MITF) independent of sumoylation. Down-regulation of PIAS3 markedly enhances RANKL-mediated osteoclastogenesis in RAW264.7 cells. Furthermore, overexpression of PIAS3 in mouse primary osteoblast (POB), down-regulates RANKL expression induced by interleukin-6 (IL-6) cytokine family, and inhibits osteoclast formation from bone marrow macrophages (BMMs) in vitro coculture system. Down-regulation of PIAS3 leads to the accelerated expression of RANKL in POB stimulated with IL-6 and soluble IL-6 receptor (sIL-6R). Taken together, our results clearly indicate that PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts.

scholarly journals Poncirin Inhibits Osteoclast Differentiation and Bone Loss through Down-Regulation of NFATc1 In Vitro and In Vivo

2020 ◽  
Vol 28 (4) ◽  
pp. 337-343
Author(s):  
Kwang-Hoon Chun ◽  
Hyun Chul Jin ◽  
Ki Sung Kang ◽  
Tong-Shin Chang ◽  
Gwi Seo Hwang
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Down Regulation

Down regulation of osteopontin interferes with HCV replication by inhibition of WNT signalling in vitro

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
C Loscher ◽  
R Bartenschlager ◽  
V Lohmann ◽  
G Tiegs ◽  
G Sass
Keyword(s):  
Wnt Signalling ◽  
Down Regulation

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Down-Regulation of UBE2T Can Enhance Irradiation Sensitivity of Osteosarcoma in Vitro and Vivo

2019 ◽  
Author(s):  
Lin Shen ◽  
Kai Zhao ◽  
Han Li ◽  
Bin Ning ◽  
Wenzhao Wang ◽  
...  
Keyword(s):  
Down Regulation

scholarly journals Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 233
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Eunguk Lim ◽  
Seokjin Hwang ◽  
Seung Hee Yun ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Osteoblastic Differentiation ◽  
Common Disease ◽  
Root Extract ◽  
Mouse Bone Marrow ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
In Vivo Experiments

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

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