Osteoclast reactive oxygen species calcium

Reactive oxygen species (ROS) and free radicals are essential for transmission of cell signals and other physiological functions. However, excessive amounts of ROS can cause cellular imbalance in reduction-oxidation reactions and disrupt normal biological functions, leading to oxidative stress, a condition known to be responsible for the development of several diseases. The biphasic role of ROS in cellular functions has been a target of pharmacological research. Osteoclasts are derived from hematopoietic progenitors in the bone and are essential for skeletal growth and remodeling, for the maintenance of bone architecture throughout lifespan, and for calcium metabolism during bone homeostasis...

Background:  Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2  nanocomposite on bone regeneration and the underlying biological mechanisms...

Reactive oxygen species (ROS) are produced by NADPH oxidase (NOX), an enzyme that reduces oxygen by using NADPH as a substrate. Apocynin (APO) is a catechol that is used as a NOX inhibitor, and N-acetyl-cysteine (NAC) can reduce intracellular ROS levels. In this work, the effect of APO and NAC on osteoclast formation were evaluated. APO and NAC significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive cells and the osteoclast area. We analyzed bone-marrow derived monocyte-macrophages (BMMs) that differentiated into osteoclasts after RANKL stimulation...

Cerium and cerium containing materials have been drawing increasing attentions in industrial and biomedical applications in recent decades. The increased applications of cerium have also increased the risk of human body exposed to cerium ions. Due to its similar ionic radius to calcium(II), cerium(III) have found mainly deposited in the skeletal system. However, the effects of cerium(III) on the bone metabolism homeostasis remain poorly understood. In the present study, the effect of cerium(III) on the osteoclastogenesis which plays a pivotal role in bone metabolism homeostasis was investigated...

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug...

UNLABELLED: Xanthotoxin (XAT) is extracted from the seeds of Ammi majus. Here, we reported that XAT has an inhibitory effect on osteoclastogenesis in vitro through the suppression of both receptor activator of nuclear factor-κB ligand (RANKL)-induced ROS generation and Ca(2+) oscillations. In vivo studies showed that XAT treatment decreases the osteoclast number, prevents bone loss, and restores bone strength in ovariectomized mice. INTRODUCTION: Excessive osteoclast formation and the resultant increase in bone resorption activity are key pathogenic factors of osteoporosis...

Heme oxygenase-1 (HO-1) has long been considered to be an endogenous antioxidant. However, the role of HO-1 is highly controversial in developing metabolic diseases. We hypothesized that HO-1 plays a role in maintaining bone mass by alleviating a redox imbalance. We investigated its role in bone remodeling. The absence of HO-1 in mice led to decreased bone mass with elevated activity and number of OCs, as well as higher serum levels of reactive oxygen species (ROS). HO-1, which is constitutively expressed at a high level in osteoclast (OC) precursors, was down-regulated during OC differentiation...

Iron is essential for osteoclast differentiation, and iron overload in a variety of hematologic diseases is associated with excessive bone resorption. Iron uptake by osteoclast precursors via the transferrin cycle increases mitochondrial biogenesis, reactive oxygen species production, and activation of cAMP response element-binding protein, a critical transcription factor downstream of receptor activator of NF-κB-ligand-induced calcium signaling. These changes are required for the differentiation of osteoclast precursors to mature bone-resorbing osteoclasts...

Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H(2)O(2)) in MC3T3-E1 cells and a murine ovariectomized (OVX) osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0...

Osteoclast maturation and function primarily depend on receptor activator of NF-κB ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca(2+)](i)) oscillation. However, the coordination mechanism that mediates Ca(2+) oscillation during osteoclastogenesis remains ill defined. Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca(2+) oscillation during osteoclastogenesis. We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation...

The precise mechanism of how TNF-α promotes osteoclast formation is not clear. Previous reports show TNF-α targets molecules that regulate calcium signaling. Inositol-1,4,5-trisphosphate receptors (IP3Rs) are important calcium channel responsible for evoking intracellular calcium oscillation. We found that TNF-α increased the expression of IP3R1 and promoted osteoclastogenesis in RANKL-induced mouse BMMs. Phosphatidylcholine-specific phospholipase C (PC-PLC) specific inhibitor D609 eliminated the upregulation of IP3R1 by TNF-α, and decreased the autoamplification of nuclear factor of activated T-cells 1 (NFATc1), thus resulted in less osteoclasts formation...

Wear debris-induced osteolysis, a major contributing factor of orthopedic implant aseptic loosening, affects long-term survival of orthopedic prostheses following joint replacement and revision surgery. Pathogenic effects of wear debris on various cell types including macrophages/monocytes, osteoblasts, and osteoclasts have been well studied. However, the interactions between wear debris particles and osteocytes, which make up over 90% of all bone cells, have not been clearly illustrated. Here, we explored the biological effects of endotoxin-free beta-tricalciumphosphate (β-TCP) wear particles with the average diameter of 1...

Liquiritigenin is one of the flavonoids present in Glycyrrhizae radix. In the present study, the effects of liquiritigenin on the function of osteoblastic MC3T3-E1 cells were studied. Liquiritigenin caused a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, and glutathione content in the cells (P<0.05). Moreover, liquiritigenin significantly decreased the production of reactive oxygen species (ROS) and osteoclast differentiation inducing factors such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and receptor activator of nuclear factor-κB ligand (RANKL) in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as a ROS generator...

Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH-oxidase. In the present study, the effect of apocynin on the function of osteoblastic MC3T3-E1 cells was studied. Apocynin caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and mineralization in the cells (P<0.05). Antimycin A (AMA), which inhibits complex III of the electron transport system, has been used as a reactive oxygen species (ROS) generator in biological systems...

RANKL (receptor activator of NF-kappaB ligand) induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca(2+) ([Ca(2+)](i)). The [Ca(2+)](i) oscillations activate calcineurin, which activates the transcription factor NFATc1. The pathway by which RANKL induces [Ca(2+)](i) oscillations and osteoclastogenesis is poorly understood. Here we report the discovery of a novel pathway induced by RANKL to cause a long lasting increase in reactive oxygen species (ROS) and [Ca(2+)](i) oscillations that is essential for differentiation of bone marrow-derived monocytes into osteoclasts...

Treatment of various types of cells with the mitochondrial ATP-sensitive K+ channel (mK(ATP)) opener has been shown to precondition cells to subsequent injuries and inhibit apoptosis. We exposed cultured osteoblastic MC3T3-E1 cells to hydrogen peroxide (H2O2) with or without pretreatment with a mK(ATP) opener, diazoxide. A marked decrease in osteoblast viability was evident after 48 h exposure of 0.3mM H2O2, compared with vehicle-treated cells. Diazoxide (0.001 approximately 10 microM) treatment significantly (P<0...

Osteoclasts are the primary cells that resorb bone; they require high energy levels to degrade bone matrix, releasing minerals to maintain calcium homeostasis. Recent work on osteoclast differentiation and activity highlights an important role for mitochondrial biogenesis and explores the role of iron transferrin in generating a positive osteoclastogenic feedback loop.

Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) homologues have been suggested to regulate osteoclast differentiation. However, no bone abnormalities have been documented in Nox1 deficient, Nox2 deficient, or Nox3 mutant mice. During receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts, mRNA levels of Nox enzymes (Nox1-4) and their adaptor proteins were monitored by real-time reverse transcriptase PCR...

Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts...

OBJECTIVE: We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis. METHODS AND RESULTS: We investigated ROS production and effects of antioxidants tempol and lipoic acid (LA) in calcification progression in rabbits given 0.5% cholesterol diet +10(4) IU/d Vit.D2 for 12 weeks. Superoxide and H2O2 microfluorotopography and 3-nitrotyrosine immunoreactivity showed increased signals not only in macrophages but preferentially around calcifying foci, in cells expressing osteoblast/osteoclast, but not macrophage markers...