• 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)
  • Recently, we found that the T. procumbens flavonoids (TPF) significantly suppressed the RANKL-induced osteoclasts differentiation and bone resorption. (biomedcentral.com)
  • Recently, we found the inhibitory effects of the TPF on osteoclast differentiation bone resorption. (biomedcentral.com)
  • We show that H3 monomethylation at lysine 27 (H3K27me1) is essential for MMP-9-dependent H3NT proteolysis during RANKL-induced osteoclast differentiation. (biomedcentral.com)
  • Through the recognition of H3K27me1 mark, MMP-9 localizes and generates H3NT proteolysis at the genes encoding osteoclast differentiation factors. (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)
  • 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)
  • In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. (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)
  • Osteopetrosis is a clinical syndrome characterized by the failure of osteoclasts to resorb bone. (medscape.com)
  • Although human osteopetrosis is a heterogeneous disorder encompassing different molecular lesions and a range of clinical features, all forms share a single pathogenic nexus in the osteoclast. (medscape.com)
  • General counseling of patients with osteopetrosis should be offered on appropriate lifestyle modifications to prevent fractures as well as genetic counseling to allow appropriate family planning. (medscape.com)
  • To understand the etiology of osteopetrosis, it is very essential to understand the bone-remodeling cycle and the cell biology of osteoclasts. (medscape.com)
  • Osteopetrosis is characterised by increased BMD, and failure of osteoclastic bone resorption due to mutations in genes that encode proteins that are essential for osteoclast activity like the chloride pump and proton pump, or mutations in genes like cathepsin K, which breakdown bone matrix. (biomedcentral.com)
  • Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. (nih.gov)
  • SAR114137, a Cathepsin S inhibitor, did not progress past phase I for chronic pain. (wikipedia.org)
  • In 2022, STI-1558, a Cathepsin L inhibitor, received FDA clearance to begin phase I studies to treat COVID-19. (wikipedia.org)
  • • Amura Holdings Ltd. , of Cambridge, UK, said preclinical study results showed that oral administration of the firm's cathepsin K inhibitor compounds resulted in sustained and potent reduction of serum bone turnover biomarkers, which clinically correlates with a significant reduction in fracture rates. (bioworld.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)
  • Description: Osteoclast-mediated bone resorption inhibitor. (gemini-genomics.com)
  • The cysteine cathepsins have attracted significant research effort as drug targets. (wikipedia.org)
  • Cathepsin K, a member of a large family of cysteine peptidases, is an enzyme that breaks down the collagen bone matrix as part of a normal biological process. (bioworld.com)
  • 2013) exhibited the elevated expression of cysteine protease (cathepsin B alone or with uPAR) in glioblastomas, which in turn was responsible of self-renewal of malignant glioblastoma stem cells. (globaltechbiz.com)
  • Thus, osteoclasts may be able to remove bone that is generated by endochondral ossification at a fast enough rate such that there is no net bone length increase. (heightquest.com)
  • A way to test this is with osteoclast inhibitors however articular cartilage endochondral ossification is slow and osteoclasts are needed for many functions. (heightquest.com)
  • 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)
  • Five cyclic peptides show inhibitory activity towards human cathepsins L, B, H, and K. Several inhibitors have reached clinical trials, targeting cathepsins K and S as promising therapeutics for osteoporosis, osteoarthritis, and chronic pain. (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 B may function as a beta-secretase 1, cleaving amyloid precursor protein to produce amyloid beta. (wikipedia.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)
  • 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)
  • Cathepsin K is involved in osteoporosis, a disease in which a decrease in bone density causes an increased risk for fracture. (wikipedia.org)
  • From a clinical standpoint, advances in knowledge about the genetic basis of bone disease offers the prospect of developing new markers for assessing fracture risk and the identification of new molecular targets that will form the basis for the design of new treatments. (biomedcentral.com)
  • Furthermore, the observation that subjects with osteopenia also showed a significant increase in cathepsin Z mRNA compared to non-osteoporotic controls, strongly suggests that if replicated in a larger study, the cathepsin Z mRNA in patients' PBMC preparations could form the basis of a test for osteoporosis , which could aid in the detection of osteoporosis before a critical and expensive fragility fracture occurs. (gertitashkomd.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)
  • Cathepsins have a vital role in mammalian cellular turnover. (wikipedia.org)
  • Cathepsin K is the most potent mammalian collagenase. (wikipedia.org)
  • Due to the limited availability of genetic models in exploring the function of Rev-erbβ, the role of Rev-erbα in mammalian circadian and metabolic physiologies is comparatively well-known. (molcells.org)
  • In contrast, osteoclasts are derived from the monocyte/macrophage lineage. (medscape.com)
  • 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)
  • The expression of cathepsin K in cultured endothelial cells is regulated by shear stress. (wikipedia.org)
  • l-Homocysteine-induced cathepsin V mediates the vascular endothelial infl ammation in hyperhomocysteinaemia. (krasgmu.ru)
  • Cathepsins B and L are involved in matrix degradation and cell invasion. (wikipedia.org)
  • Cathepsin K, among other cathepsins, plays a role in cancer metastasis through the degradation of the extracellular matrix. (wikipedia.org)
  • [ 8 ] Acidification promotes solubilization of the bone mineral in the sealing zone, and various proteases, notably cathepsin K, catalyze degradation of the matrix proteins. (medscape.com)
  • The genetic knockout for cathepsin S and K in mice with atherosclerosis was shown to reduce the size of atherosclerotic lesions. (wikipedia.org)
  • Authors found a strong correlation of elevated levels of Cathepsin Z mRNA in patients with osteopenia in addition to those with osteoporosis. (gertitashkomd.com)
  • Since these cell lineages produce the protease , cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. (gertitashkomd.com)
  • Irrespective of the biological effects of cathepsin Z, it has now been shown for the FIRST TIME here that the increase in cathepsin Z mRNA in isolated PBMC fractions is very strongly diagnostic for osteoporosis, at least in the patient group studied. (gertitashkomd.com)
  • Cathepsin Z mRNA has been shown for the first time to be significantly elevated in the PBMCs of patients with either osteopenia or osteoporosis compared to non-osteoporotic controls. (gertitashkomd.com)
  • However, the increase in cathepsin Z mRNA level in osteopenia/osteoporosis was also observed when male and female participants over the age of 50, or female participants over the age of 50 were analysed. (gertitashkomd.com)
  • All of these genes play a role in the RANK signalling pathway, which is essential for osteoclast activation. (biomedcentral.com)
  • Osteoclasts are the bone resorbing cells of the body, and they secrete cathepsin K in order to break down collagen, the major component of the non-mineral protein matrix of the bone. (wikipedia.org)
  • Mouse cathepsin L is homologous to human cathepsin V. Mouse cathepsin L has been shown to play a role in adipogenesis and glucose intolerance in mice. (wikipedia.org)
  • Cathepsin L-deficient mice were shown to have less adipose tissue, lower serum glucose and insulin levels, more insulin receptor subunits, more glucose transporter (GLUT4) and more fibronectin than wild type controls. (wikipedia.org)
  • The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. (wikipedia.org)
  • The defective CLCN7 gene encodes a chloride channel that is apparently important in osteoclast function. (msdmanuals.com)
  • Thus, we cannot rule out entirely the possibility that cathepsin Z levels are, in part, a function of age for all participants. (gertitashkomd.com)
  • No influence was found between genetic polymorphisms of osteoprotegerin in patients with diabetes and periodontitis. (bvsalud.org)
  • Stroke Traumatic brain injury Alzheimer's disease Arthritis Ebola, Cathepsin B and to a lesser extent cathepsin L have been found to be necessary for the virus to enter host cells. (wikipedia.org)
  • Cathepsin K has also been shown to play a role in arthritis. (wikipedia.org)
  • 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)
  • Cathepsin zymography separates different cathepsins based on their migration through a polyacrylamide gel co-polymerized with a gelatin substrate. (wikipedia.org)
  • Understanding of the mechanisms that integrate energy metabolism in the entire organism has significantly improved with the application of contemporary biochemical tools for quantifying the fuel substrate metabolism with cutting-edge mouse genetic procedures. (mdpi.com)
  • In fact in a genetic disease where osteoclast formation is suppressed, the shape of the long bones is almost "post-like" with no reduction in mid-shaft cross-sectional area. (heightquest.com)
  • And, in ends of the bones not formed by growth plates don't have as large a cross-sectional area favoring absorption thus apposition at the ends of the bones is greater than osteoclast resorption. (heightquest.com)
  • You could elevate HGH levels which increases both bone formation and resorption thus allowing you to safely lower osteoclast levels. (heightquest.com)
  • XP is a severe genetic disease carrying a very high predisposition to skin cancers caused by severe burns when patients are exposed to UV light. (bioworld.com)
  • Cathepsin B has also been implicated in the progression of various human tumors including ovarian cancer. (wikipedia.org)
  • Bone diseases are a common cause of morbidity and mortality in developed countries, and genetic factors play an important role in the pathogenesis of these diseases. (biomedcentral.com)
  • Environmental factors such as diet and exercise influence BMD but genetic factors play a predominant role, accounting for up to 85% of the variation in peak BMD. (biomedcentral.com)
  • To additional characterize the pathological bone forma tion inside the chondrocytic locations from the arch centra, we ana lyzed osteoclast exercise. (pkc-inhibitors.com)
  • These results for cathepsin Z mRNA as a single biomarker are comparable to a peripheral blood biomarker panel consisting of 10 mRNAs including cathepsin Z mRNA for diagnosis of ischaemic stroke. (gertitashkomd.com)
  • Cathepsin L degrades fibronectin, insulin receptor (IR), and insulin-like growth factor 1 receptor (IGF-1R). (wikipedia.org)
  • Perhaps the larger cross-sectional area of the epiphysis formed by growth plate growth facilitates osteoclast absorption. (heightquest.com)
  • Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)
  • Osteoclasts can tightly attach to the bone matrix by integrin receptors to form a sealing zone, within which is a sequestered, acidified compartment. (medscape.com)