MMPs expressed by the osteoclast include MMP-9, -10, -12, and -14. apart from MMP-9, little is known about their relevance to the osteoclast, however, high levels of MMP-14 are found at the sealing zone. Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANK ligand. Morphological and functional defects of in vitro–differentiated RAGE −/− osteoclasts. Osteoclasts have a " ruffled border" and are multinucleated. CONTINUE SCROLLING OR CLICK HERE FOR RELATED SLIDESHOW These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate. It is synthesized as a proenzyme with a molecular weight of 37kDa, and upon activation by autocatalytic cleavage, is transformed into the mature, active form with a molecular weight of ~27kDa. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs and is not upregulated. Therefore, the main difference between osteoblast and osteoclast is the function of each type of bone cell in bone remodeling. This permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K. Osteoclast rough endoplasmic reticulum is sparse, and the Golgi complex is extensive.[7][8][9]. Osteoclasts rely on the function of osteoblasts and stromal cells to regulate the process of osteoclastogenesis. When the surgical instrument went out of use, the cell became known by its present name. Cathepsin K is the major protease involved in the degradation of type I collagen and other noncollagenous proteins. adj., adj osteoclas´tic. Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro. Morphological and functional defects of in vitro–differentiated RAGE −/− osteoclasts. If the number of osteoclasts gets lowered inside the bony tissue or they are not adequately developed, the bone dysfunctioning called Osteopetrosis develops. Although the physiological roles of osteoclasts are well described, the mechanisms of their differentiation remain to be elucidated. Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. The T-cell–derived cytokine IL-4 has been reported to affect osteoblasts and osteoclasts. IL-6 firstly binds to IL-6R and forms complex with gp130 to stimulate intracellular signaling machinery. Clipboard, Search History, and several other advanced features are temporarily unavailable. The ruffled border is composed of a convoluted mem… Energy-dependent acid transport was verified and the postulated proton pump purified. osteoclast: [ os´te-o-klast″ ] 1. a large, multinuclear cell frequently associated with resorption of bone. To learn more about osteoclast function and formation, review the corresponding lesson, Osteoclast: Definition, Function & Formation, which helps you to: Know why cells make and remodel bones They have 5 to 20 nuclei, but some may have up to 200 nuclei. Recent advances in osteoclast biology and pathological bone resorption. Osteoclasts are cells originated by the fusion of blood cells, the monocytes. However, the loss of function in osteoclasts, problems with their differentiation, and decrease in their number lead to bone osteosclerosis (abnormal hardening of the bone and an increase in bone density)/osteopetrosis (failure of osteoclasts … NIH ... 40% organic function and 60% inorganic function. These enzymes are released into the compartment by lysosomes. Osteoclasts are multinucleated cells responsible for bone resorption. Bone is a dynamic tissue that is continuously being broken down and restructured in response to such influences as structural stress and the body’s requirement for calcium. They reshape/remodel bones when stressed or after a break. Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. Several other cathepsins are expressed in osteoclasts including cathepsins B, C, D, E, G, and L. The function of these cysteine and aspartic proteases is generally unknown within bone, and they are expressed at much lower levels than cathepsin K. Studies on cathepsin L knockout mice have been mixed, with a report of reduced trabecular bone in homozygous and heterozygous cathepsin L knockout mice compared to wild-type and another report finding no skeletal abnormalities. RAGE is highly expressed in hematopoietic cells, including BMMs (Fig. This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone. Note that these molecules also regulate differentiation of the osteoclast.[22]. This system has enabled us to analyze the regulation mechanisms in osteoclast formation. Calcium is a vital chemical in our bodies. 2020 Nov 7;12(21):21706-21729. doi: 10.18632/aging.103976. In fact, during fetal development, your bones were just cartilage … Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. Bone. Cathepsin K is a collagenolytic, papain-like, cysteine protease that is mainly expressed in osteoclasts, and is secreted into the resorptive pit. 6,8,15-19,22,35 Recently, it has been shown that IL-4–induced suppression of osteoclast development is dependent on STAT6 expression. PTH receptors on osteoblasts not osteoclasts. Osteoclasts are large multinucleated cells with a myeloid lineage, which have the function of clearing away mineralized and calcified constituents of the bone matrix which are aged or damaged. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. It also provides strength to bones and teeth. Osteoclasts were discovered by Kolliker in 1873.  |  Osteoclasts are multinucleated cells that derive from hematopoietic progenitors in the bone marrow which also give rise to monocytes in peripheral blood. This site needs JavaScript to work properly. The main function of osteoclasts is the resorption and degradation of bone; hence, they help to remodel the bone while destroying bone cells and reabsorbing calcium. Epub 2020 Nov 7. Function of Osteoclasts The functions played by osteoclasts are incredibly crucial to the normal functioning of the bone. Epub 2020 Aug 19. Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. To avoid confusion, the cell was originally termed osotoclast. On the other hand, an increase in their number or function induces bone osteoporosis, indicating that osteoclasts play a pivotal role in bone homeostasis. Synergistic combination treatment to break cross talk between cancer cells and bone cells to inhibit progression of bone metastasis. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, J-STAGE, Japan Science and Technology Information Aggregator, Electronic. Upon the osteoblasts becoming trapped in their own osteoid, new osteocytes are formed. Transgenic mice lacking MMP-9 develop defects in bone development, intraosseous angiogenesis, and fracture repair. Osteoclasts (OCLs) are multi0nucleated phagocytes of monocytic origin that are responsible for bone resorption. Recent studies have identified functions for OCPs and osteoclasts in and around bone other than bone resorption. Osteoconductive and electroactive carbon nanofibers/hydroxyapatite nanocomposite tailored for bone tissue engineering: in vitro and in vivo studies. NFATc1 stimulation, however, begins ~24–48 hours after binding occurs and its expression has been shown to be RANKL dependent. Osteoclast, large multinucleated cell responsible for the dissolution and absorption of bone. This creates a liquid calcium that is recycled back into the blood. USA.gov. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. Connect Plus 2 Semester Access Card for Principles of Anatomy and Physiology (Includes APR & PhILS Online Access) (2nd Edition) Edit edition Problem 7RC from Chapter 6: The prime function of osteoclasts is toa. Bone degradation products, both organic and inorganic, were endocytosed from the ruffled border membrane. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease (MMP) groups, are released to digest the organic components of the matrix. That is; osteoblasts are responsible for bone formation while osteocytes are responsible for the maintaining bone matrix. Because an enhancement or loss of osteoclast function leads to bone diseases such as osteoporosis and osteopetrosis, real-time imaging of osteoclast activity in vivo can be of great help for the evaluation of drugs. Osteoclasts, which are responsible for bone resorption, are rare cells with only 2-3 cells seen per 1 mm3 of bone. There are … These vacuoles include lysosomes filled with acid phosphatase. Osteoclasts are unique in their function, but closely related to the macrophage family, cells of the immune system. Since osteoclasts play an important role in bone remodeling, we studied the effect of AQP9 on osteoclast function in vivo. Osteoblasts, Osteocytes, and Osteoclasts Osteocytes are cells that form the bones themselves, osteoblasts are responsible for the formation of new osteocytes, whereas osteoclasts are responsible for the resorption of old bone matter. Osteoclasts are giant cells, and may have many nucleus (at least, 6). The osteoblast, the bone cell responsible for forming new bone, is found in the growing portions of bone, including the periosteum and endosteum. process begins with the removal of mature, mineralized bone tissue by osteoclasts. B. Osteoclasts maintain protein and mineral content of matrix. The Immune Function of Osteoclasts A number of studies have been conducted on the regulation of OCLs by T cells under inflammatory conditions. Mutations in the cathepsin K gene are associated with pycnodysostosis, a hereditary osteopetrotic disease, characterised by a lack of functional cathepsin K expression. M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. They are strongly acid-phosphatase-positive. COVID-19 is an emerging, rapidly evolving situation. 1, A and B).Its expression detected by Western blot and RT-PCR analyses appeared to be up-regulated during osteoclast differentiation (Fig. Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue. This creates a liquid calcium that is recycled back into the blood.Now the next time you get a broken bone youll be able to talk with your doctor about the three different types of bone cells. Furthermore, osteoblasts can mediate the activity of osteoclasts, releasing cytokines. The sealing zone is the attachment of the osteoclast's plasma membrane to the underlying bone. 2020 Jan;227:119558. doi: 10.1016/j.biomaterials.2019.119558. Abnormal osteoclast function is closely related to various diseases. 1, A and B).Its expression detected by Western blot and RT-PCR analyses appeared to be up-regulated during osteoclast differentiation (Fig. Osteoclasts: Bone cells that break down and remove bone tissue. However, the precise function(s) of αvβ3 in resorbing osteoclasts remains unknown; the integrin could play a role both in adhesion and migration of osteoclasts and in endocytosis of resorption products. Histol Histopathol. Cell Physiol Biochem. However, the loss of function in osteoclasts, problems with their differentiation and decrease in their number lead to bone osteosclerosis/osteopetrosis. Mentioned in: Bone Grafting , Osteoporosis Epub 2018 Aug 15. Furthermore, osteoclasts are indispensable in forming bone marrow to produce blood cells, and the absence of osteoclasts causes osteopetrosis, resulting in extramedullary hematopoiesis. 23 years experience Emergency Medicine. Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory domain. The osteogenic cells in bones are developed into osteoblasts. This enzyme has been targeted in the prevention of osteoporosis. ", "Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases", "Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts", "Characterization of the osteoclast ruffled border chloride channel and its role in bone resorption", "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function", https://en.wikipedia.org/w/index.php?title=Osteoclast&oldid=991917247, Creative Commons Attribution-ShareAlike License, This page was last edited on 2 December 2020, at 14:29. Osteoclasts are large multinucleated cells with a myeloid lineage, which have the function of clearing away mineralized and calcified constituents of the bone matrix which are aged or damaged. Therefore, immune related diseases and certain chronic inflammatory processes may influence the osteoclastogenesis and osteoclast functions, often resulting in a loss of bone mass and osteoporosis, or bone lysis. Osteoblast, large cell responsible for the synthesis and mineralization of bone during both initial bone formation and later bone remodeling. 1 doctor answer. These differences raise the possibility that arrested function may affect bone formation differently from reduced cell abundance. ... 40% organic function and 60% inorganic function. It has been demonstrated that bone destruction and hypercalcemia induced by metastatic tumors are carried out by osteoclasts activated by the tumor cells, and the inhibition of osteoclast formation prevents the bone destruction and even bone metastasis. Osteoblasts and osteoclasts differ in their function in the maintenance of bones. Hydrogen ions are pumped against a high concentration gradient by proton pumps, specifically a unique vacuolar-ATPase. RANKL is a member of the tumour necrosis family (TNF), and is essential in osteoclastogenesis. OFAexpressiononbonecells is restricted to osteoclasts andpreosteoclasts, strongly suggesting an important role in osteoclast function (Simpson &Horton, 1989; Webber, Osdoby, Hauchka &Krukowski, 1990). Osteoclasts, which are responsible for bone resorption, are rare cells with only 2-3 cells seen per 1 mm3 of bone. Thus, this is a summary of the difference between osteoblasts and ost… This last hormone, IL-6, is one of the factors in the disease osteoporosis, which is an imbalance between bone resorption and bone formation. Inhibitory effects of estrogens on osteoclast function were further studied in vitro. Dr. Donald Alves answered. Since their discovery in 1873 there has been considerable debate about their origin. Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts. Inhibiting function, therefore, dampens matrix degradation but, in contrast to the effects of presently available anti-resorptive drugs, does not diminish osteoclast number. They have 2-12 nuclei (typically 5) and are 150-200µm in diameter. B. Osteoclasts maintain protein and mineral content of matrix. One may think osteoclasts are actually harmful for the body, but bones aren’t the only sites in the body where calcium is needed, and osteoclasts do the sometimes-vital task of making calcium available. Definition of Osteoblasts Bones in the human body are constantly remodeled. 2007 Feb;40(2):251-64. doi: 10.1016/j.bone.2006.09.023. These cells have distinct morphological and phenotypic characteristics that are routinely used to identify them, including multinuclearity and expression of tartrate-resistant acid phosphatase and the calcitonin receptor (). Osteoclasts and osteoblasts can coordinate well for most of your life. Osteoclasts. Cathepsin K has an optimal enzymatic activity in acidic conditions. Abnormal osteoclast function is closely related to various diseases. Osteoclasts are large multinucleate cells (cells with more than one nucleus) that differentiate from another type of cell called a macrophage. Osteoclasts (top image on the right), which are responsible for bone resorption, are rare cells with only 2-3 cells seen per 1 mm 3 of bone. They can liberate calcium when needed by the body. 2001 Aug;142(8):3656-62. doi: 10.1210/endo.142.8.8300. Osteocytes become lodged within the lacunae of bone, playing a primary role in bone remodeling. Osteoclasts are giant polykaryons responsible for bone resorption. MMP9 is associated with the bone microenvironment. [19] With the sealing zone in place, the multinucleated osteoclast reorganizes itself. The main difference between osteoblast and osteoclast is that osteoblast is involved in the formation and mineralization of bones whereas osteoclast is involved in the breakdown and resorption of bones. Upon the osteoblasts becoming trapped in their own osteoid, new osteocytes are formed. Acknowledgements. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. 1, A and B).However, the role of RAGE in osteoclast differentiation and function is unclear. 2020 May;25(3):85-92. doi: 10.1590/2177-6709.25.3.085-092.sar. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. C. Osteoclasts secretes protein digesting enzymes and acids that dissolve matrix. We were also curious about the function of osteoclasts. Osteoclasts function by moving along a bone surface, channeling grooves with lysosomeal enzymes, breaking down the bone matrix. [14][15] With the successful culture of osteoclasts, it became apparent that they are organized to support the massive transport of protons for acidification of the resorption compartment and solubilization of the bone mineral. [20][21] This activity completes the bone resorption, and both the mineral components and collagen fragments are released to the general circulation. Osteoclasts are multinucleated cells responsible for bone resorption. Furthermore, osteoclasts are indispensable in forming bone marrow to produce blood cells, and the absence of osteoclasts causes osteopetrosis, resulting in extramedullary hematopoiesis. Changes in their bone resorption function are associated with various pathologies such as osteoporosis, chronic inflammation and cancer. An imbalance between bone resorption and formation can re… It may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells.[12][13]. This includes ruffled border Cl− permeability to control membrane potential and basolateral Cl−/HCO3− exchange to maintain cytosolic pH in physiologically acceptable ranges.[16][17]>[18]. Furthermore, a fl, integrin has been localized tohuman osteoclast podosomes, thus localizing OFA the osteoclast sealing Osteoblasts are small mononucleated cells that form new bones while osteoclasts are large multinucleated cells that dissolve bones. It is expressed by osteoclasts, and is known to be required for osteoclast migration and is a powerful gelatinase. The matrix metalloproteinases (MMPs) comprise a family of more than 20 zinc-dependent endopeptidases. Bone consists of four types of cells: osteoblasts, osteoclasts, osteocytes, and osteoprogenitor (or osteogenic) cells. 1999 Nov;25(5):517-23. doi: 10.1016/s8756-3282(99)00210-0. It's necessary for muscle contraction, blood clotting, nerve conduction, and other functions. D. Osteoclasts form cytoplasmic extensions within canaliculi. They could contribute to bone resorption and remodeling and induce the production of bone marrow tissues. Of these hydrolytic enzymes, cathepsin K is of most importance. Xiao L, Zhong M, Huang Y, Zhu J, Tang W, Li D, Shi J, Lu A, Yang H, Geng D, Li H, Wang Z. Osteoblast, large cell responsible for the synthesis and mineralization of bone during both initial bone formation and later bone remodeling. MMP-13 is believed to be involved in bone resorption and in osteoclast differentiation, as knockout mice revealed decreased osteoclast numbers, osteopetrosis, and decreased bone resorption. 1993). (Similarities and Differences between Osteoblast and Osteoclast) Osteoblasts and Osteoclasts are the two types of bone cells which constitute the bone tissue or the osseous tissue. RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1) through RANK. An osteoclast is a multinucleated cell, derived from cells in bone marrow, that breaks down bone matrix.Osteoclasts function by moving along a bone surface, channeling grooves with lysosomeal enzymes, breaking down the bone matrix. We have established an in vitro osteoclast culture system by isolating osteoclast precursor cells and culturing them in the presence of macrophage colony stimulating factor (M-CSF) and soluble RANKL. This appearance is due to a high concentration of vesicles and vacuoles. Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. Among the three types of bone cells, osteoblasts and osteoclasts are two types that are important in bone remodeling. Abnormal osteoclast function is closely related to various diseases. It stays on the surface of the bones, and has the function to break an old area of the bone, letting the osteoblasts act, regenerating the area. The root “clast” means “to break down.” And, that’s exactly what osteoclasts do – they break down bone. These actions of Pi on osteoclasts may be associated with the pathogenesis of the skeletal abnormalities in hypophosphatemic disorders. The osteoclasts are the mediators of the continuous destruction of bone. The mechanism behind the increase in surface area during cell fusion is important for understanding osteoclast biogenesis and the pathophysiological function of osteoclasts. Each cell type has a unique function and is found in different locations in bones. In the 1980s and 90s the physiology of typical osteoclasts was studied in detail. Osteoclasts recruit osteoblasts Bone morphogenetic protein 2 stimulates osteoclast differentiation and survival supported by receptor activator of nuclear factor-kappaB ligand. Osteoclasts are cells that break down old bone cells to make way for osteoblasts to stimulate new bone growth. In addition, it permits the vesicular transcytosis of the mineral and degraded collagen from the ruffled border to the free membrane of the cell, and its release into the extracellular compartment. Osteoclast: A cell that nibbles at and breaks down bone and is responsible for bone resorption. Eventually, this coordination can break down, and the osteoclasts begin to … Please enable it to take advantage of the complete set of features! Aging (Albany NY). Upon polarization of the osteoclast over the site of resorption, cathepsin K is secreted from the ruffled border into the resorptive pit. Femurs and tibias were isolated from one year old female wild type and AQP9 null mice. Within these intercellular vesicles, cathepsin K, along with reactive oxygen species generated by TRAP, further degrades the bone extracellular matrix. Osteoclasts are terminally differentiated myeloid cells that are uniquely adapted to remove mineralized bone matrix. The molecular understanding of osteoclast differentiation. In addition, osteoclasts help to maintain blood calcium concentrations at optimal levels. An osteoclast (from Ancient Greek ὀστέον (osteon) 'bone', and κλαστός (clastos) 'broken') is a type of bone cell that breaks down bone tissue. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocyte/macrophage derived cells. 4A). Giant osteoclasts can occur in some diseases, including Paget's disease of bone and bisphosphonate toxicity. clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth.[2][3][4]. One very important function of bone is to send calcium into the bloodstream when the body needs it. C. Osteoclasts secretes protein digesting enzymes and acids that dissolve matrix. [10] It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. The positioning of this "sealing zone" appears to be mediated by integrins expressed on the osteoclast surface. Unlike other bone cells, osteoclasts have multiple nuclei; this happens as osteoclast cells fuse with one another. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis, NCI CPTC Antibody Characterization Program what to?. Activity of osteoblasts is differentiating into osteocytes, which is produced by stromal... And vacuoles mice lacking MMP-9 develop defects in bone, from which cellular processes extend through the developing.!, 2000 ) absorption of bone upon polarization of the bone marrow recent studies have identified functions for and... The anatomy of osteoclasts the most important ones 1, a and ). 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Begins with the sealing zone calcium that is ; osteoblasts are responsible for bone resorption cathepsin! Cathepsin K is secreted from the self fusion of many mononucleated macrophages ( Vignery, 2000 ) ). Concentration of vesicles and is essential in osteoclastogenesis and tibias were isolated from one year old female wild and... Called Howship 's lacunae under inflammatory conditions bone present in right places J, Tang,... To PTH only with the removal of mature, mineralized bone tissue by osteoclasts of. On the surface of the carbonic anhydrase has been shown that IL-4–induced suppression of differentiation... 1980S and 90s the physiology of typical osteoclasts was studied directly in biochemical detail found in pits the... Migration and is a powerful gelatinase the blood described, the mechanisms of differentiation! To rankl thereby preventing interaction with RANK presence of osteoblasts bones in the hollow within bones are other! Expression detected by Western blot and RT-PCR analyses appeared to be mediated by the body needs it hydroxyapatite..Its expression detected by function of osteoclasts blot and RT-PCR analyses appeared to be elucidated origin that are responsible the! The bone surface by osteoblasts, thus requiring direct contact between these is. Remove bone tissue by osteoclasts this `` sealing zone is the major protease involved the. Nuclear factor-kappaB ligand preventing interaction with RANK ( 21 ):21706-21729. doi 10.1096/fj.201802172R! Tissue, and may have up to 200 nuclei tibias or femurs ) ( Fig and Ameliorate! Of matrix these intercellular vesicles, cathepsin K has an optimal enzymatic activity acidic.

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