The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption

2015 ◽  
Vol 6 (10) ◽  
pp. 3351-3358 ◽  
Author(s):  
Wei-Jie Wu ◽  
Min Seuk Kim ◽  
Byung-Yong Ahn
Keyword(s):  
Bone Resorption ◽  
Vitamin K ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect

Vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

scholarly journals Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

2019 ◽  
Vol 6 (6) ◽  
pp. 190360 ◽  
Author(s):  
Liuliu Yan ◽  
Lulu Lu ◽  
Fangbin Hu ◽  
Dattatrya Shetti ◽  
Kun Wei
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Giant Cells ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
And Function

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

scholarly journals Inhibitory effect of omega-3 fatty acids on alveolar bone resorption and osteoclast differentiation

2020 ◽  
Vol 62 (3) ◽  
pp. 298-302 ◽  
Author(s):  
Yu Ozaki ◽  
Toshiya Morozumi ◽  
Kiyoko Watanabe ◽  
Toshizo Toyama ◽  
Haruka Sasaki ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Omega 3 Fatty Acids ◽  
Omega 3

scholarly journals Inhibition of osteoclast differentiation and bone resorption by polyunsaturated fatty acids in RAW 264.7 murine macrophages

2012 ◽  
Vol 31 (1) ◽  
Author(s):  
J. C. Boeyens ◽  
W-H. Chua ◽  
M.C. Kruger ◽  
A.M. Joubert ◽  
M. Coetzee
Keyword(s):  
Fatty Acids ◽  
Bone Resorption ◽  
Polyunsaturated Fatty Acids ◽  
Cell Line ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Raw 264.7 ◽  
Murine Macrophages

This study investigated the effects of polyunsaturated fatty acids on osteoclast formation and bone resorption in RAW 264.7 murine pre-osteoclasts. Data obtained suggests an inhibitory effect of these compounds on osteoclastogenesis and bone resorption in the cell line tested.

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.

MO058INHIBITION OF OSTEOCLAST DIFFERENTIATION BY 1.25-D AND THE CALCIMIMETIC KP2326 REVEALS 1.25-D RESISTANCE IN ADVANCED CKD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Julie Bernardor ◽  
Sacha Flammier ◽  
Bruno Ranchin ◽  
Segolene Gaillard ◽  
Diane Platel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Active Vitamin ◽  
Vitamin D Analogs ◽  
Active Vitamin D ◽  
Ckd Stage ◽  
Osteoclastic Differentiation

Abstract Background and Aims Active vitamin D analogs and calcimimetics are cornerstones for managing secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Their direct effects on bone cells remain to be determined. Method Peripheral blood mononuclear cells (PBMCs) of 19 pediatric CKD patients and 6 healthy donors (HD) were differentiated into osteoclasts in presence of M-CSF and RANKL. Effect of combined or single treatment with active vitamin D (1.25-D) and/or the calcimimetic KP2326 were evaluated onto osteoclast differentiation and osteoclast mediated bone resorption. Results 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when CKD worsens. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through an activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited human osteoclast-mediated bone resorption. Conclusion Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however to a different extent. Whilst 1.25-D has no significant effect on bone resorption, KP2326 inhibits bone resorption. Recent data showed that calcimimetics also have a direct anabolic effect on bone, through the stimulation of osteoblastic differentiation and mineralization in human mesenchymal stem cells in vitro. All these results provide a strong rationale for a global positive effect of calcimimetics on bone remodeling. Calcimimetics also significantly decrease FGF23 levels. In the setting of global systematic deleterious effects of high FGF23 levels in CKD, and keeping in mind that active vitamin D analogs stimulate FGF 23 production, all these data could favor the use of decreased doses of 1.25-D with low-doses of calcimimetics in SHPT in dialysis, the combination of these two therapies already being proposed in the 2017 K-DIGO guidelines.

scholarly journals Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production

2017 ◽  
Vol 43 (4) ◽  
pp. 1425-1435 ◽  
Author(s):  
Lingbo Kong ◽  
Biao Wang ◽  
Xiaobin Yang ◽  
Hua Guo ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Signaling Pathways ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Ring Structure ◽  
Osteoclast Formation ◽  
Ros Generation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Metabolic Bone Disorder ◽  
Picrasma Quassioides

Background/Aims: Osteoporosis is a metabolic bone disorder that tortures about millions of people worldwide. Recent study demonstrated agents derived from picrasma quassioides is a promising drug for targets multiple signaling pathways. However its potential in treatment of bone loss has not been fully understood. Methods: The bone marrow macrophages (BMMs) were cultured and induced with M-CSF and RANKL followed by picrasidine I (PI) treatment. Then the effects of PI on osteoclast formation were evaluated by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Moreover, effects of PI on bone resorption activity of mature osteoclast were studied through bone resorption pit counting and actin ring structure analysis. Further, the involved potential signaling pathways cross-talking were investigated by performed Western blotting and quantitative real-time PCR examination. Results: Results demonstrated PI strongly inhibited RANKL induced osteoclast formation from its precursors. Mechanistically, the inhibitory effect of PI on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and NFATc1. Moreover, PI markedly blocked the RANKL-induced osteoclastogenesis by attenuating MAPKs and NF-κB signaling pathways. In addition, PI decreased the ROS generation in osteoclast and osteoblast. Conclusion: Taken together our data demonstrate that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.

Inhibitory effect of cantharidin on osteoclast differentiation and bone resorption

2010 ◽  
Vol 33 (3) ◽  
pp. 457-462 ◽  
Author(s):  
Myung Hee Kim ◽  
Ki Shuk Shim ◽  
Seong Hwan Kim
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect

scholarly journals Inhibitory effect of chloroquine on bone resorption reveals the key role of lysosomes in osteoclast differentiation and function

2012 ◽  
Vol 32 (5) ◽  
pp. 222-231 ◽  
Author(s):  
Md. Abdul Alim Al-Bari ◽  
Masahiro Shinohara ◽  
Yusuke Nagai ◽  
Hiroshi Takayanagi
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
And Function

scholarly journals Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass

2015 ◽  
Vol 226 (3) ◽  
pp. 121-134 ◽  
Author(s):  
Wang Xiao ◽  
Fei Beibei ◽  
Shen Guangsi ◽  
Jiang Yu ◽  
Zhang Wen ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Direct Evidence ◽  
Osteoclast Differentiation ◽  
Reactive Oxygen ◽  
Inhibitory Effect ◽  
Iron Accumulation ◽  
Oxygen Scavenger

Postmenopausal osteoporosis is a metabolic disease associated with estrogen deficiency. The results of numerous studies have revealed the positive correlation between iron accumulation and postmenopausal osteoporotic status. Although the results of previous studies have indicated that estrogen or iron alone have an effect on bone metabolism, their combined effects are not well defined. Using anin vivomouse model, we found that bone mass was minimally affected by an excess of iron in the presence of estrogen. Once the source of estrogen was removed (ovariectomy), iron accumulation significantly decreased bone mass. These effects were accompanied by fluctuations in the level of oxidative stress. To determine whether these effects were related to bone formation or bone resorption, primary osteoblasts (OBs), RAW264.7 cells, and bone-marrow-derived macrophages were used forin vitroexperiments. We found that iron accumulation did inhibit the activity of OBs. However, estrogen had little effect on this inhibition. In contrast, iron promoted osteoclast differentiation through the production of reactive oxygen species. Estrogen, a powerful reactive oxygen scavenger, suppressed this effect in osteoclasts. Our data provided direct evidence that iron affected the bone mass only in the absence of estrogen. The inhibitory effect of estrogen on iron-induced osteopenia was particularly relevant to bone resorption rather than bone formation.

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