Human cathepsin osteoclasts. Medical search. Frequent questions

Recently, Th17 was reported to express RANKL itself as well as directly inducing mature osteoclasts via cell-to-cell contact, substantiating its role in inflammatory bone destruction [ 6 ]. (hindawi.com)
Elevated cIAP Species AMPAR3 mRNA expression in AIA patella was restored to typical by NBQX, and coincided with enhanced mRNAs reflecting osteoclast activation (RANKL), bone resorption ( Pim MedChemExpress Cathepsin K) and bone formation (COL1A1). (adenosine-receptor.com)
Cathepsin K and RANKL mRNA levels and RANKL to OPG ratios had been decreased by NBQX. (adenosine-receptor.com)
Therefore, the protective effect of NBQX in AIA may perhaps reflect inhibition of osteoblast activity connected with decreased RANKL mediated activation of osteoclasts. (adenosine-receptor.com)
On the other hand, NBQX may possibly also target AMPA and KA GluRs expressed by synoviocytes56 and chondrocytes57 to regulate RANKL or directly inhibit osteoclast activity.46 In conclusion, a single intra-articular injection of NBQX alleviated inflammation, discomfort and joint degeneration in rat AIA. (adenosine-receptor.com)
In turn, MM cells-derived RANKL causes the upregulation of its receptor, RANK, and Notch2 in pre-osteoclasts. (oncotarget.com)
Notch2 stimulates osteoclast differentiation by promoting autocrine RANKL signaling. (oncotarget.com)
Osteoclasts and odontoclasts are multinucleated cells derived from hematogenous bone marrow, from the monocyte/macrophage cell lineage, and are formed by the fusion of these cells under the action of colony stimulating factor 1 (CSF-1), macrophage colony stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1) and RANKL (receptor activator of nuclear factor kappa-B ligand), which also have a role in chemotaxis and cell differentiation [1]. (oatext.com)
The differentiation of the osteoclast precursor into a mature osteoclast requires RANKL binding to its receptor RANK (receptor activator of nuclear factor kappa-B). However, OPG binding to RANKL will block RANKL binding to RANK, which will result in inhibition of osteoclastogenesis (Figure 1) [3]. (oatext.com)
SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-¿B ligand (RANKL) in CD11b+ mouse bone marrow cells. (vectorbiolabs.com)
Osteoclast differentiation of Pdk4 / bone marrow derived monocyte/macrophage lineage cells from the presence of M CSF and RANKL was suppressed, and osteoclastogenesis was impaired during the coculture of wild form BMMs and Pdk4 / osteoblasts, by which Rankl expression and promoter exercise had been decreased. (jakenzyme.com)
RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts. (nih.gov)
Human mast cells induce osteoclastogenesis through cell surface RANKL. (nih.gov)
In both cases, the cells need to be differentiated into the mature osteoclast by M-CSF and RANKL [1-4]. (sciforschenonline.org)
Recently, this cell line has become a valuable tool to study osteoclast differentiation and activity due to its expression of RANK and differentiation to osteoclast in response to RANKL [7]. (sciforschenonline.org)
We show that H3 monomethylation at lysine 27 (H3K27me1) is essential for MMP-9-dependent H3NT proteolysis during RANKL-induced osteoclast differentiation. (biomedcentral.com)
The binding of RANKL to its cognate receptor RANK on pre-osteoclast cell membrane stimulates the expression of key determinants of osteoclast differentiation such as NF-κB, c-Fos, and NFATc1 at the early stage of the process [ 1 , 8 ]. (biomedcentral.com)
The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). (molcells.org)
Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo . (molcells.org)
Currently, the clinical interventions for patients with BC-bone metastasis (BC-BM) are bisphosphonates (BPs) or denosumab (an anti-receptor activator of nuclear factor kappa B ligand (RANKL) monoclonal antibody), which disrupt the vicious cycle by targeting osteoclasts [ 6 ]. (biomedcentral.com)

The inhibitory effect of RGE on Th17 differentiation and osteoclastogenesis observed in mice was also confirmed in the subsequent experiments performed using human peripheral blood mononuclear cells. (hindawi.com)
By comparing the TB signature with gene expression profiles from human breast metastases and an in vitro osteoclast model, we demonstrate that our model mimics both the human breast cancer bone microenvironment and osteoclastogenesis. (biomedcentral.com)
Here we present evidences that MM can efficiently drive osteoclastogenesis by contemporaneously activating Notch signaling on tumor cells and osteoclasts through the aberrant expression of Notch ligands belonging to the Jagged family. (oncotarget.com)
Such synergism between tumor cells and pre-osteoclasts in MM-induced osteoclastogenesis can be disrupted by silencing tumor-derived Jagged1 and 2. (oncotarget.com)
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+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. (cusabio.com)

Within the osteolytic lesions of bone metastases, tumor cells interact with osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells), thereby inhibiting normal bone development and ultimately leading to bone destruction [ 1 - 4 ]. (biomedcentral.com)
ALP optimistic osteoblasts and TRAP reactive osteoclasts were abundant at the subchondral bone in arthritic samples, whilst control ones depicted fewer osteoclasts and weakly stained ALP constructive osteoblasts, suggesting stimulated bone turnover during the arthritic group. (jakenzyme.com)
Bone is a highly dynamic organ that is continuously remodeled by coordinated activities of two cell types, osteoclasts and osteoblasts [ 1 , 2 ]. (biomedcentral.com)
Osteoblasts are mononucleated mesenchymal stem cells that form bone matrix, whereas osteoclasts are bone-resorbing multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage [ 3 , 4 , 5 ]. (biomedcentral.com)
In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. (molcells.org)
Bone is a unique connective tissue which constantly undergoes remodeling, which involves bone formation by osteoblasts and bone resorption by osteoclasts[ 3 ]. (ijbs.com)
However, active bone remodeling with osteoclasts and osteoblasts working in synchrony continues to occur. (elsevier.es)

The protein encoded by this gene is a cysteine cathepsin, a lysosomal cysteine protease involved in bone remodeling and resorption. (wikipedia.org)
Cathepsin B, also known as CTSB, is a lysosomal cysteine protease. (biolegend.com)

This protein, which is a member of the peptidase C1 protein family, is expressed predominantly in osteoclasts. (wikipedia.org)

SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. (vectorbiolabs.com)
Paraffin sections were utilized for alkaline phosphatase, tartrate resistant acid phosphatase, cathepsin K, MMP 1, kind II collagen, CTX II and fibronectin staining assessments. (jakenzyme.com)

In human/mouse DR5-transgenic Ubc.Cre mice with CIA, transgenic DR5 was most highly expressed on CD11b+ macrophages, with lower expression on CD4+ T cells. (nih.gov)
In human/mouse DR5-transgenic LysM.Cre mice, transgenic DR5 was restrictively expressed on macrophages. (nih.gov)
The anti-human DR5 antibody TRA-8 was efficacious in reducing the severity of arthritis via targeted depletion of macrophages and immunomodulation. (nih.gov)
Although these protocols provide a successful method to culture osteoclasts from RAW264.7 cells, they don't express the issue of having multinucleated cells such as macrophages mixing with osteoclasts in the population. (sciforschenonline.org)

On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. (vectorbiolabs.com)
Finally, transcriptome sequencing of 11β-HSD1 knock in osteoclast progenitor cells indicated the Hippo pathway1 was mostly enriched. (ijbs.com)

This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. (nih.gov)
Osteoclast differentiation and activation factor. (cusabio.com)

OC destroys the mineral and collagen matrix by secreting matrix metalloproteinases (MMPs), cathepsin K (CtsK), H + and Cl − , and eventually forming bone lacunae. (frontiersin.org)
Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. (mayabouchenaki.com)
In regular creating salmon vertebrae, these places are modeled by endochondral bone formation, a process requiring invasion of osteoclasts and action of TRAP, Mmps and Cathepsin K. Transcription of mmps are up regulated during IDD and compres sion induced IVD in mammals. (pkc-inhibitors.com)

Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. (nih.gov)
Dysregulation of osteoclasts can cause bone diseases such as osteopetrosis and osteoporosis. (sciforschenonline.org)

Absence of osteoclasts visualized as a result of TRAP staining was characteristic dur ing the advancement of vertebral fusions, indicating that regular endochondral ossification was restrained. (pkc-inhibitors.com)
It has been shown that multinucleated foreign body giant cells also express tartrateresistant acid phosphatase (TRAP) [14], hence, classical TRAP staining is unable to distinguish between macrophage polykaryons and osteoclasts. (sciforschenonline.org)

In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. (molcells.org)

Once migrated to the bone marrow, MM cells unbalance bone formation and resorption via the recruitment and maturation of osteoclast precursors. (oncotarget.com)

Cathepsin K is a protease, which is defined by its high specificity for kinins, that is involved in bone resorption. (wikipedia.org)
Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses. (wikipedia.org)
Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface. (biomedcentral.com)
The possible mechanisms involved in osteoclasts recruitment from external granuloma and various dentin resorption patterns in internal root resorption will be discussed based on a case in which the upper lateral incisor with a history of pulp necrosis treated endodontically, developed an internal root resorption in association with external granuloma. (oatext.com)
Bone resorption is initiated by osteoclasts and resorption of hard dental structures by odontoclasts. (oatext.com)
Osteoclasts recruitment and activation, and angiogenesis in maxillary alveolar processes in internal root resorption associated with external granuloma. (oatext.com)
Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment. (vectorbiolabs.com)
Bone resorption occurs mainly on the bone surface, by the osteoclasts (OC) on bone metabolism in continuous absorption. (frontiersin.org)
Osteoclasts are multinucleated cells that are essential for bone resorption and regulate bone remodeling. (sciforschenonline.org)
BC-BMs mostly are osteolytic metastases that are characterized by aberrant bone destruction caused by increased osteoclasts-mediated bone resorption in the tumor-bone interface [ 10 ]. (biomedcentral.com)

To determine the therapeutic efficacy and immunomodulatory effect of an anti-human death receptor 5 (DR5) antibody, TRA-8, in eliminating macrophage subsets in a mouse model of type II collagen-induced arthritis (CIA). (nih.gov)
A human/mouse-chimeric DR5-transgenic mouse, under the regulation of a mouse 3-kb promoter and a loxP-flanked STOP cassette, was generated and crossed with an ubiquitous Cre (Ubc.Cre) mouse and a lysozyme M-Cre (LysM.Cre)-transgenic mouse to achieve inducible or macrophage-specific expression. (nih.gov)
Osteoclast, derived from macrophage-mononuclear lineage, is a special myeloid cell. (frontiersin.org)
They don't often exclusively differentiate into osteoclast but also into other multinucleated cells as well including macrophage polykaryons. (sciforschenonline.org)
However, osteoclasts and macrophage polykaryons are almost indistinguishable under a light microscope (TRAP+ with three or more nuclei). (sciforschenonline.org)
nevertheless, we are able to identify the optimal conditions at which osteoclasts are found to be more than macrophage polykaryons. (sciforschenonline.org)
Finally, this article also demonstrates that osteoclasts and macrophage polykaryons can be distinguished by immunofluorescence staining for cathepsin K. (sciforschenonline.org)
Osteoclasts can be obtained by isolating primary bone marrow monocytes or by using macrophage cell lines. (sciforschenonline.org)
Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix. (uni-freiburg.de)

Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters. (uni-bielefeld.de)

Cathepsin K inhibitors show great potential in the treatment of osteoporosis. (wikipedia.org)
Merck had a cathepsin K inhibitor, odanacatib, in Phase III clinical trials for osteoporosis. (wikipedia.org)
In conclusion, our study demonstrated the role of 11β-HSD1 in facilitating osteoclasts formation and maturation through the Hippo signaling, which is a new therapeutic target to manage osteoporosis. (ijbs.com)

Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. (wikipedia.org)

Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene. (wikipedia.org)

Medivir has a cathepsin K inhibitor, MIV-711 (L-006235), in Phase IIa clinical trial, as a disease modifying osteoarthritis drug, as of October 2017. (wikipedia.org)
Characterization of the gene expression signature specific to the TB interface in our model revealed signaling mechanisms operative in human breast cancer metastases and predicted a therapeutic inhibitor of cancer-mediated osteolysis. (biomedcentral.com)
By using RNAi and small molecule inhibitor approaches, we also confirmed that G9a is the major methyltransferase to catalyze H3K27me1 for MMP-9-dependent H3NT proteolysis and trigger the expression of osteoclast-specific genes. (biomedcentral.com)

The RAW264.7 cell line is most commonly used to study osteoclast differentiation and its signaling pathways. (sciforschenonline.org)
These factors then initiate multiple signal transduction pathways to turn on downstream genes and activate quiescent osteoclast precursor (OCP) cells to become mature osteoclasts [ 1 , 8 ]. (biomedcentral.com)

This study was undertaken to investigate the effects of red ginseng extracts (RGE) on autoimmune arthritis in mice and humans and to delineate the underlying mechanism. (hindawi.com)
Therefore, RGE can ameliorate arthritis in mice with CIA by targeting pathogenic Th17 and osteoclast differentiation, suggesting a novel therapy for treatment of RA. (hindawi.com)
Chicken type II collagen was used to induce CIA in mice, which were then treated with an anti-human DR5 antibody, TRA-8. (nih.gov)
In this study, we observed increased 11β-HSD1 expression in osteoclasts within an osteoporotic mice model (ovariectomized mice). (ijbs.com)
Furthermore, specifically knock out 11β-HSD1 in osteoclasts, by crossing cathepsin-cre mice with 11β-HSD1 flox/flox mice, presented significant protecting effect of skeleton when they underwent ovariectomy surgery. (ijbs.com)

Control monkeys showed faint immunoreactivity against cathepsin K and MMP 1 in cells covering the articular cartilage and synovial tissues, indicating physiological amounts of collagenous degradation. (jakenzyme.com)

In vitro experiments showed the endogenous high expression of 11β-HSD1 lead to osteoclast formation and maturation. (ijbs.com)

Human joints are complicated structures formed by synovial tissues, articular cartilage and subchondral bone tissue. (jakenzyme.com)

Cathepsin K antibodies are marketed for research into expression of this enzyme by various cells. (wikipedia.org)
Finally, MM cells through Jagged ligands expression can also activate Notch signaling in pre-osteoclast by direct contact. (oncotarget.com)
showed that the osteoclastic potential of mandibular bone marrow stromal cells and the number of osteoclasts are higher compared to long-bone marrow stromal cells [2]. (oatext.com)
Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots. (mpg.de)
Mouse Cathepsin B, amino acids (His18-Phe339) (Accession# P10605), with C-terminal 10x His tag, was expressed in CHO cells. (biolegend.com)
Currently published protocols of culturing RAW264.7 cells often assume multinucleated cells that have three or more nuclei with distinguished osteoclast characteristics (such as TRAP+) as osteoclasts. (sciforschenonline.org)

Osteoclasts and their activity are key regulators of bone formation. (sciforschenonline.org)
Meanwhile, we found 11β-HSD1 facilitated mature osteoclasts formation inhibited bone formation coupled H type vessel (CD31 hi Emcn hi ) growth through reduction of PDFG-BB secretion. (ijbs.com)
Then, by suppression of YAP expression in Hippo signaling, we observed the redundant of osteoclasts formation even in 11β-HSD1 high expression conditions. (ijbs.com)

In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets. (biomedcentral.com)
The defective CLCN7 gene encodes a chloride channel that is apparently important in osteoclast function. (msdmanuals.com)
It is uncommon, frequently lethal, and often due to a mutation in the osteoclast-associated gene TCIRG1 . (msdmanuals.com)

Other cathepsin K inhibitors are in various stages of development. (wikipedia.org)
Which of these reactions are physiologically or pathophysiologically relevant is often not clear, although studies on knockout animals, human genetic and epigenetic, as well as biochemical studies using natural or synthetic inhibitors have provided insight to a great extent. (evelinvahter.com)

Cathepsin K expression is stimulated by inflammatory cytokines that are released after tissue injury. (wikipedia.org)

Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Annexin A11 (ANXA11) in Tissue homogenates and other biological fluids. (jsce-ip.com)
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Galectin 4 (GAL4) in samples from Serum, plasma, tissue homogenates and other biological fluids with no significant corss-reactivity with analogues from other species. (jsce-ip.com)

1. Dilute the recombinant mouse Cathepsin B to 10 μg/ml in activation buffer (25 mM MES, 1 mM DTT, pH 5.0) and incubate the protein at 25°C for 3 min. (biolegend.com)

That the expression of cathepsin K is characteristic for some cancers and not others has been documented. (wikipedia.org)

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. (vectorbiolabs.com)

For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. (molcells.org)

Believing for the similarities of typical joints in humans and monkeys, we've employed a model of collagen induced arthritis in Macaca fascicularis in an attempt to assess the histological Metastatic carcinoma alterations caused by such situation inside the extracellular matrix of your articular cartilage. (jakenzyme.com)

While most cathepsins are exclusively endopeptidases, CTSB exhibits both carboxypeptidase and endopeptidase activities. (biolegend.com)

The ED50 as determined by its ability to bind Human TNFRSF11B in functional ELISA is less than 10 ug/ml. (cusabio.com)

In this review, we will give an overview of 23 members of the human MMP family and describe functions, linkages to disease and structural and mechanistic features. (evelinvahter.com)

Another large gap in our understanding of osteoclastogenic transcription program is the identification of chromatin factors that have the potential to link specific aspects of chromatin function to osteoclast differentiation processes. (biomedcentral.com)

The activity of Cathepsin B is determined by its ability to cleave the fluorogenic peptide substrate, Z-Leu-Arg-AMC (Z=Benzyloxycarbonyl, and AMC=7-amino-4-methylcoumarin) after activation. (biolegend.com)
During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation. (cusabio.com)

Alkaline phosphatase activity in human periodontal ligament: age effect and relation to cementum growth rate. (shengsci.com)

A single intra-articular injection of combined iGluR antagonists didn't have an effect on cartilage erosion in CFA arthritis.27 Even though memantine (NMDAR antagonist) alleviated synovitis and joint pathology in CIA, continual 12-hourly intraperitoneal administration in the drug was needed.21 Because AMPA/KA GluRs localised to remodelling bone in human OA, RA and rat AIA, we quantified GluR and bone cell mRNAs in joint tissues. (adenosine-receptor.com)

Co-purified gelatinases alter the stability and biological activities of human plasma fibronectin preparations. (shengsci.com)

Through the recognition of H3K27me1 mark, MMP-9 localizes and generates H3NT proteolysis at the genes encoding osteoclast differentiation factors. (biomedcentral.com)

Anatomy16

Organisms2

Diseases9

Chemicals and Drugs57

Analytical, Diagnostic and Therapeutic Techniques and Equipment15

Phenomena and Processes23

Disciplines and Occupations1

Information Science3

RANKL20

Osteoclastogenesis5

Osteoblasts7

Cysteine protease2

Predominantly in osteoclasts1

Tartrate-resistant a2

Macrophages4

Progenitor cells2

Differentiation and activation2

MMPs3

Osteopetrosis2

TRAP2

Osteoblast1

Precursors1

Resorption10

Macrophage9

Lysosomal1

Osteoporosis3

Receptor1

CTSK1

Inhibitor3

Pathways2

Mice5

Immunoreactivity1

Maturation1

Subchondral1

Cells6

Formation3

Gene3

Inhibitors2

Inflammatory1

Antibody2

Protein1

Characteristic1

Expression1

Behavior1

Matrix1

Exclusively1

Functional1

Functions1

Processes1

Activation2

Activity1

Arthritis1

Fibronectin1

Genes1