scholarly journals Stimulation of Resorption in Cultured Mouse Calvarial Bones by Thiazolidinediones

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4349-4361 ◽  
Author(s):  
A. M. Schwab ◽  
S. Granholm ◽  
E. Persson ◽  
B. Wilkes ◽  
U. H. Lerner ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stimulation Of

Dosage-dependent release of 45Ca was observed from prelabeled mouse calvarial bones after treatment with two thiazolidinediones, troglitazone and ciglitazone. Release of 45Ca by ciglitazone was decreased by the osteoclast inhibitors acetazolamide, calcitonin, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, and IL-4, but not affected by the peroxisome proliferator-activated receptor γ antagonist, GW 9662, the mitotic inhibitor, hydroxyurea, or indomethacin. Enhanced expression of receptor activator of nuclear factor-κB ligand (RANKL) mRNA and protein and decreased osteoprotegerin (OPG) mRNA and protein were noted after ciglitazone treatment of calvariae. Ciglitazone and RANKL each caused increased mRNA expression of osteoclast markers: calcitonin receptor, tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase-9, integrin β3, and nuclear factor of activated T cells 2. OPG inhibited mRNA expression of RANKL stimulated by ciglitazone, mRNA expression of osteoclast markers stimulated by ciglitazone and RANKL, and 45Ca release stimulated by troglitazone and ciglitazone. Increased expression of IL-1α mRNA by ciglitazone was not linked to resorption stimulated by the thiazolidinedione. Ciglitazone did not increase adipogenic gene expression but enhanced osteocalcin mRNA in calvariae. In addition to exhibiting sensitivity to OPG, data indicate that stimulation of osteoclast differentiation and activity by thiazolidinediones may occur by a nonperoxisome proliferator-activated receptor γ-dependent pathway that does not require cell proliferation, prostaglandins, or IL-1α but is characterized by an increased RANKL to OPG ratio.

scholarly journals Optimized Extract from Corylopsis coreana Uyeki (Hamamelidaceae) Flos Inhibits Osteoclast Differentiation

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Yongjin Lee ◽  
Jung-Eun Kim ◽  
Kwang-Jin Kim ◽  
Seung-Sik Cho ◽  
Young-Jin Son
Keyword(s):  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Alcoholic Extract ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Fractures Of The Spine ◽  
The Stability

Osteoporosis is a metabolic disorder that decreases the stability against fractures of the spine, femur, and radius by weakening the strength and integrity of bones. Receptor activator of nuclear factor-kappa B ligand signaling ultimately activated nuclear factor-activated T cells c1, a major transcription factor for osteoclast formation. This study researched the effects of Corylopsis coreana (C. coreana) Uyeki flos extracts on the antiosteoclastic potential of macrophages and the phytochemicals contained therein. The alcoholic extract of C. coreana Uyeki flos inhibited the differentiation of osteoclast. We carried out the experiments of the pattern of differentiation of osteoclasts based on the alcoholic percentage of extracts. Among them, 80% alcoholic extract showed the highest inhibitory effect. The alcoholic extract was composed of phytochemicals such as bergenin, quercetin, and quercitrin. This extract inhibited not only mRNA expression levels of NFATc1, osteoclast-associated receptor (OSCAR), cathepsin K, and tartrate-resistant acid phosphatase (TRAP), but also the translational expression of NFATc1. The inhibitory effect for osteoclast differentiation of the alcoholic extract was confirmed using the resorption pit assay. This is the first scientific report of the antiosteoclastic effects of C. coreana Uyeki flos extract, which can be applied therapeutically for the treatment of osteoporosis.

scholarly journals Spi-C positively regulates RANKL-mediated osteoclast differentiation and function

2020 ◽  
Vol 52 (4) ◽  
pp. 691-701 ◽  
Author(s):  
Eun Mi Go ◽  
Ju Hee Oh ◽  
Jin Hee Park ◽  
Soo Young Lee ◽  
Na Kyung Lee
Keyword(s):  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Specific Domain ◽  
Receptor Activator ◽  
And Function

Abstract Spi-C is an SPI-group erythroblast transformation-specific domain transcription factor expressed during B-cell development. Here, we report that Spi-C is a novel receptor activator of nuclear factor-κB ligand (RANKL)-inducible protein that positively regulates RANKL-mediated osteoclast differentiation and function. Knockdown of Spi-C decreased the expression of RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1, receptor activator of nuclear factor-κB (RANK), and tartrate-resistant acid phosphatase (TRAP), resulting in a marked decrease in the number of TRAP-positive multinucleated cells. Spi-C-transduced bone marrow-derived monocytes/macrophages (BMMs) displayed a significant increase in osteoclast formation in the presence of RANKL. In addition, Spi-C-depleted cells failed to show actin ring formation or bone resorption owing to a marked reduction in the expression of RANKL-mediated dendritic cell-specific transmembrane protein and the d2 isoform of vacuolar (H+) ATPase V0 domain, which are known osteoclast fusion-related genes. Interestingly, RANKL stimulation induced the translocation of Spi-C from the cytoplasm into the nucleus during osteoclastogenesis, which was specifically blocked by inhibitors of p38 mitogen-activated protein kinase (MAPK) or PI3 kinase. Moreover, Spi-C depletion prevented RANKL-induced MAPK activation and the degradation of inhibitor of κB-α (IκBα) in BMMs. Collectively, these results suggest that Spi-C is a novel positive regulator that promotes both osteoclast differentiation and function.

scholarly journals Nasturtium officinale Extract Suppresses Osteoclastogenesis in RAW 264 Cells by Inhibiting IκB-Kinase β

2021 ◽  
Vol 16 (6) ◽  
pp. 1934578X2110206
Author(s):  
Yukino Tsunekage ◽  
Masatoshi Takeiri ◽  
Yuri Yoshioka ◽  
Shinichi Matsumura ◽  
Yoshihide Kimura ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Specific Inhibitor ◽  
Nuclear Factor Κb ◽  
Bone Diseases ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Nasturtium Officinale ◽  
Iκb Kinase

Osteoclasts are large, multinucleated, bone-absorbing cells and play a crucial role in osteolytic bone diseases such as osteopetrosis and rheumatoid arthritis. Therefore, controlling osteoclast differentiation and activation has been considered a promising strategy to prevent and treat osteolytic diseases. In this study, we demonstrate, using the mouse monocyte-derived macrophage-like cell line RAW 264, that extract from Nasturtium officinale or watercress, an herb of European origin, suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro . N. officinale extract decreased the emergence of tartrate-resistant acid phosphatase-positive differentiated multinuclear cells and inhibited their bone-absorbing activity. The extract decreased expression of genes associated with osteoclast differentiation and function. Induction of nuclear factor of activated T cells c1 (NFATc1), the master transcriptional regulator of osteoclastogenesis, was blunted by N. officinale extract. Activation of nuclear factor-κB and mitogen-activated protein kinases pathways, both of which are necessary for NFATc1 induction and osteoclast differentiation, was also suppressed by the extract. Among upstream kinases, activity of IκB-kinase β (IKKβ), but not that of TGFβ-activated kinase 1, was inhibited by N. officinale extract in vitro. Pharmacological inhibition of IKKβ by a specific inhibitor PS1145 in RAW 264 cells mostly recaptured the inhibitory action of N. officinale extract. These findings provide a novel pharmacological action of N. officinale and its potential usefulness for the prevention of osteoporosis.

scholarly journals HDAC9 Inhibits Osteoclastogenesis via Mutual Suppression of PPARγ/RANKL Signaling

2015 ◽  
Vol 29 (5) ◽  
pp. 730-738 ◽  
Author(s):  
Zixue Jin ◽  
Wei Wei ◽  
HoangDinh Huynh ◽  
Yihong Wan
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Hormone Receptors ◽  
Ex Vivo ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulatory Loop

Abstract Recent studies suggest that the class II histone deacetylase (HDAC)9 plays important roles in physiology such as metabolism and immunity. Here, we report that HDAC9 also controls bone turnover by suppressing osteoclast differentiation and bone resorption. HDAC9 expression is down-regulated during osteoclastogenesis. Ex vivo osteoclast differentiation is accelerated by HDAC9 deletion but diminished by HDAC9 overexpression. HDAC9 knockout mice exhibit elevated bone resorption and lower bone mass. Bone marrow transplantation reveal that the osteoclastogenic defects are intrinsic to the hematopoietic lineage, because the excessive bone resorption phenotype can be conferred in wild-type (WT) mice receiving HDAC9-null bone marrow, and rescued in HDAC9-null mice receiving WT bone marrow. Mechanistically, HDAC9 forms a negative regulatory loop with peroxisome proliferator-activated receptor gamma (PPARg) and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. On one hand, PPARγ and nuclear factor κB suppress HDAC9 expression, on the other hand, HDAC9 inhibits PPARγ activity in synergy with silencing mediator of retinoic acid and thyroid hormone receptors (SMRT)/NCoR corepressors. These findings identify HDAC9 as a novel, important and physiologically relevant modulator of bone remodeling and skeletal homeostasis.

Complement C1q production by osteoclasts and its regulation of osteoclast development

2012 ◽  
Vol 447 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Boon Heng Dennis Teo ◽  
Yuri V. Bobryshev ◽  
Boon King Teh ◽  
Siew Heng Wong ◽  
Jinhua Lu
Keyword(s):  
Lupus Erythematosus ◽  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Detection Methods ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Blood Monocytes ◽  
Activated T Cells ◽  
Cellular Origin

C1q deficiency is the strongest known risk factor for SLE (systemic lupus erythematosus) but its endogenous cellular origin remains limitedly understood. In the present study we investigate the production of C1q by both cultured and endogenous bone osteoclasts. Blood monocytes were cultured with RANKL (receptor activator of nuclear factor κB ligand) and M-CSF (macrophage colony-stimulating factor) to generate osteoclasts and these cells expressed C1Q mRNA and also secreted C1q protein. Intracellular C1q was detectable in developing osteoclasts at day 3 by Western blotting and was also detectable by flow cytometry. By immunofluorescence microscopy, C1q was preferentially detected in immature osteoclasts. By multiple detection methods, C1q expression was markedly increased after IFNγ (interferon γ) treatment. By immunohistochemistry, C1q was also detected in endogenous bone osteoclasts. When osteoclasts were cultured on immobilized C1q, these cells exhibited 2–7-fold increases in the expression of signature osteoclast genes [TRAP (tartrate-resistant acid phosphatase), cathepsin K, calcitonin receptor, carbonic anhydrase II and NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1)], suggesting an osteoclastogenic capability. This is the first report of C1q production by osteoclasts. Its ability to enhance osteoclast development implies reduced osteoclastogenesis in patients with SLE as they often experience decreased C1q levels. This is consistent with the non-erosive nature of lupus arthritis.

scholarly journals Isofraxidin Inhibits Receptor Activator of Nuclear Factor-κB Ligand–Induced Osteoclastogenesis in Bone Marrow–Derived Macrophages Isolated from Sprague–Dawley Rats by Regulating NF-κB/NFATc1 and Akt/NFATc1 Signaling Pathways

2021 ◽  
Vol 30 ◽  
pp. 096368972199032
Author(s):  
Wei Wang ◽  
Bo Wang
Keyword(s):  
Bone Marrow ◽  
Signaling Pathways ◽  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Luciferase Reporter ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Receptor Activator

Osteoporosis is a common bone disease that is characterized by decreased bone mass and fragility fractures. Isofraxidin is a hydroxy coumarin with several biological and pharmacological activities including an anti-osteoarthritis effect. However, the role of isofraxidin in osteoporosis has not yet been investigated. In the present study, we used receptor activator of nuclear factor-κB ligand (RANKL) to induce osteoclast formation in primary bone marrow macrophages (BMMs). Our results showed that RANKL treatment significantly increased tartrate-resistant acid phosphatase (TRAP) activity, as well as the expression of osteoclastogenesis-related markers including MMP-9, c-Src, and cathepsin K at both mRNA and protein levels; however, these effects were inhibited by isofraxidin in BMMs. In addition, luciferase reporter assay demonstrated that isofraxidin treatment suppressed the RANKL-induced an increase in nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) transcriptional activity. Besides, the decreased expression level of IκBα and increased levels of p-p65, p-IκBα, and p-Akt in RANKL-induced BMMs were attenuated by isofraxidin. Moreover, NFATc1 overexpression rescued the anti-osteoclastogenic effect of isofraxidin with increased expression levels of MMP-9, c-Src, and cathepsin K. Taken together, these findings indicated that isofraxidin inhibited RANKL-induced osteoclast formation in BMMs via inhibiting the activation of NF-κB/NFATc1 and Akt/NFATc1 signaling pathways. Thus, isofraxidin might be a therapeutic agent for the treatment of osteoporosis.

scholarly journals The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 479 ◽  
Author(s):  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Ariadna Pielok ◽  
Mateusz Sikora ◽  
Lukas Valihrach ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Nuclear Factor ◽  
Paracrine Signaling ◽  
Receptor Activator ◽  
The Impact

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

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