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Encyclopedia > Osteoclast
Osteoclast
Osteoblasts and osteoclasts on trabecula of lower jaw of calf embryo.
Gray's subject #18 88
Dorlands/Elsevier o_08/12600400

An osteoclast (from the Greek words for "bone" and "broken") is a type of bone cell that removes bone tissue by removing the bone's mineralized matrix. This process is known as bone resorption. Osteoclasts and osteoblasts are instrumental in controlling the amount of bone tissue. Osteoblasts form bone; osteoclasts resorb bone. Osteoclasts are formed by the fusion of cells of the monocyte-macrophage cell line.[1] Osteoclasts are characterized by high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K. Image File history File links Gray81. ... Elseviers logo. ... Grays Anatomy illustration of a human femur. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ... Bone resorption is the process by which osteoclasts break down bone and release the minerals. ... An osteoblast (from the Greek words for bone and to build) is a mononucleate cell which produces a protein that produces osteoid. ... Monocyte A monocyte is a leukocyte, part of the human bodys immune system that protect against blood-borne pathogens and move quickly to sites of infection in the tissues. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, makros = long, phagein = eat) are white blood cells, more specifically phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. ... Protein expression is a subcomponent of gene expression. ... Tartrate resistant acid phosphatase is a glycosylated monomeric metalloenzyme expressed in mammals (1). ...

Contents

Morphology

Osteoclast displaying many nuclei within its "foamy" cytoplasm
Osteoclast displaying many nuclei within its "foamy" cytoplasm

An osteoclast is a large cell that is characterized by multiple nuclei and a cytoplasm with a homogenous, "foamy" appearance. This appearance is due to a high concentration of vesicles and vacuoles.[2][3] At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", which touches the bony surface.[4] The ruffled border facilitates removal of the bone matrix. The mineral portion of the matrix (called hydroxyapatite) includes calcium and phosphate ions. These ions are absorbed into small vesicles (see endocytosis) which move across the cell and eventually are released into the extracellular fluid, through a "secretory domain", thus increasing levels of the ions in the blood. The ruffled border indicates osteoclast activation and serves to increase surface area for bone resorption. Image File history File links Osteoclast. ... Image File history File links Osteoclast. ... This article or section is in need of attention from an expert on the subject. ... Vacuoles are large membrane-bound compartments within some eukaryotic cells where they serve a variety of different functions: capturing food materials or unwanted structural debris surrounding the cell, sequestering materials that might be toxic to the cell, maintaining fluid balance (called turgor) within the cell, exporting unwanted substances from the... Hydroxylapatite is a naturally occurring form of calcium apatite with the formula Ca5(PO4)3(OH), but is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two molecules. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Atomic mass 40. ... Above is a ball-and-stick model of the inorganic hydrogenphosphate anion (HPO42−). Colour coding: P (orange); O (red); H (white). ... This article or section is in need of attention from an expert on the subject. ... Endocytosis is a process whereby cells absorb material (molecules such as proteins) from the outside by engulfing it with their cell membrane. ... In some animals, including mammals, the two types of extracellular fluids are interstitial fluid and blood plasma. ...


Formation

Osteoclasts formation requires the presence of RANK ligand (receptor activator of nuclear factor κβ) and M-CSF (macrophage-colony stimulating factor). These membrane bound proteins are produced by neighbouring stromal cells and osteoblasts; thus requiring direct contact between these cells and osteoclast precursors. In cell biology, stromal cells are connective tissue cells of an organ found in the loose connective tissue. ... An osteoblast (from the Greek words for bone and to build) is a mononucleate cell that produces a protein that produces osteoid. ... First Impressions Precursors is an upcoming science fiction/first person shooter game made by Deep Shadows studio, based in Ukraine. ...


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. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocyte/macrophage derived cells. Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... A Second messenger system is a method of cellular signaling where the signalling molecule does not enter the cell, but rather utilizes a cascade of events that transduces the signal into a cellular change. ... Differentiation can mean the following: In biology: cellular differentiation; evolutionary differentiation; In mathematics: see: derivative In cosmogony: planetary differentiation Differentiation (geology); Differentiation (logic); Differentiation (marketing). ...


RANKL is a member of the tumour necrosis family (TNF), and is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1) through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs, and is not upregulated. NFATc1 stimulation, however, begins ~24-48 hours after binding occurs and its expression has been shown to be RANKL dependent. This article lacks information on the importance of the subject matter. ... In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Osteopetrosis is an extremely rare inherited disorder whereby the bones harden, becoming denser. ... Look up Rank in Wiktionary, the free dictionary Generally, rank is a system of hierarchy used to classify like things. ...


Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which binds to RANKL thereby preventing interaction with RANK.


Function

Once activated, they move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in a small cavity called Howship's lacuna, formed from the digestion of the underlying bone. The sealing zone is the attachment of the osteoclast's plasmalemma to the underlying bone. Sealing zones are bounded by belts of specilized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin. The osteoclast releases hydrogen ions (H2O + CO2HCO3- + H+) through the ruffled border into the cavity, acidifying and dissolving the mineralized bone matrix into Ca2+, H3PO4, H2CO3 and water. Hydrogen ions are pumped against a high concentration gradient by proton pumps, specifically a unique vacuolar-ATPase. This enzyme has been targeted in the prevention of osteoporosis. 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. These enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance. Chemotaxis is a kind of taxis, in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. ... The cell membrane (also called the plasma membrane or plasmalemma) is a semipermeable lipid bilayer common to all living cells. ... Grays Anatomy illustration of a human femur. ... Podosomes are the primary sites of integrin stimulated actin polymerization in leukocytes of the monocytic lineage. ... In an unbranched, chain-like biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or fold within the chain, which appears also in a variety of other molecules. ... Osteopontin is a glycoprotein first identified in 1986 in osteoblasts. ... Hydronium is the common name for the cation H3O+. Nomenclature According to IUPAC ion nomenclature, it should be referred to as oxonium. ... This article describes water from a scientific and technical perspective. ... Carbon dioxide is a chemical compound composed of one carbon and two oxygen atoms. ... In inorganic chemistry, a bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. ... Hydronium is the common name for the cation H3O+. Nomenclature According to IUPAC ion nomenclature, it should be referred to as oxonium. ... Grays Anatomy illustration of a human femur. ... In biology, the word matrix is used for the material between animal or plant cells, or generally the material (or tissue) in which more specialized structures are embedded, and also specifically for one part of the mitochondrion. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Atomic mass 40. ... A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment, thereby creating a difference or gradient in both pH and electrical charge (ignoring differences in buffer capacity) and tending to establish an electrochemical potential. ... ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. ... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... Hydrolytic enzymes break down protein, carbohydrate, and fat molecules into their simplest units. ... A cathepsin is a type of protease, ie a type of protein that breaks apart other proteins. ... In biology, the word matrix is used for the material between animal or plant cells, or generally the material (or tissue) in which more specialized structures are embedded, and also specifically for one part of the mitochondrion. ... Organelles. ... A cathepsin is one of a family of proteases, a type of protein that breaks apart other proteins, found in many types of cells including those in all animals. ...


Cathepsin K is a collagenolytic, papain-like, cysteine protease that is mainly expressed in osteoclasts, and is secreted into the resorptive pit. Mutations in the cathepsin K gene are associated with pycnodysostosis, a hereditary osteopetrotic disease, characterised by lack of functional cathepsin K expression. Knockout studies of cathepsin K in mice lead to an osteopetrotic phenotype, which, is partially compensated by increased expression of proteases other that cathepsin K and enhanced osteoclastogenesis. Osteopetrosis is an extremely rare inherited disorder whereby the bones harden, becoming denser. ...


Cathepsin K has an optimal enzymatic activity in acidic conditions. 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.


In the osteoclast, cathepsin K functions in the resorptive process. Upon polarization of the osteoclast over the site of resorption, cathepsin K is secreted from the ruffled border into the resorptive pit. Here, it is the major protease involved in the degradation of type I collagen and other noncollagenous proteins, which have been demineralized by the acidic environment of the resorptive pit. From the resorptive pit, cathepsin K transmigrates across the ruffled border, through the osteoclast via intercellular vesicles and is then released by the functional secretory domain. Within these intercellular vesicles, cathepsin K, along with ROS generation by TRAP further degrades bone resorption products. Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... Reactive oxygen species (ROS) include oxygen ions, free radicals and peroxides both inorganic and organic. ... Tartrate resistant acid phosphatase is a glycosylated monomeric metalloenzyme expressed in mammals (1). ...


Numerous other cathepsins are expressed in osteoclasts. These include cathepsin 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 that 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. A knockout mouse is a genetically engineered mouse one or more of whose genes have been made inoperable. ... Trabecular bone (also known as spongy bone) is one of two main types of bone. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ...


The matrix metalloproteinases (MMPs) comprise a family of more that 20 zinc-dependent endopeptidases. The role of matrix metalloproteinases (MMPs) in osteoclast biology is ill-defined, but in other tissue they have been linked with tumor promoting activities, such as activation of growth factors and are required for tumor metastasis and angiogenesis. Growth factor is any of about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. ...


MMP-9 is associated with the bone microenvironment. It is expressed by osteoclasts, and is known to be required for osteoclast migration and is a powerful gelatinase. Transgenic mice lacking MMP-9 develop defects in bone development, intraosseous angiogenesis, and fracture repair. Cell migration is a central process in the development and maintenance of multicellular organisms. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ...


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.


MMPs expressed by the osteoclast include MMP-9, -10, -12, and -14. apart from MMP-9, little is know about their relevance to the osteoclast, however, high levels of MMP-14 are found at the sealing zone.


Regulation

Osteoclasts are regulated by several hormones, including parathyroid hormone (PTH) from the parathyroid gland, calcitonin from the thyroid gland, and growth factor interleukin 6 (IL-6). This last hormone, IL-6, is one of the factors in the disease osteoporosis, which is an imbalance between bone resorption and bone formation. Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANK ligand. Note that these molecules also regulate differentiation of the osteoclast.[5] Hormone is also the NATO reporting name for the Soviet/Russian Kamov Ka-25 military helicopter. ... Parathyroid hormone (PTH) is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. ... Calcitonin is a 32 amino acid polypeptide hormone that is produced in humans primarily by the C cells of the thyroid, and in many other animals in the ultimobranchial body. ... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily... Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. ... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... This article lacks information on the importance of the subject matter. ...


Use in orthodonture

Osteoclastic activity is also the basis for straightening of the teeth with dental braces. The pressure exerted on the periodontal ligament of the tooth (by the braces) causes osteoclasts to absorb the alveolar bone. Osteoblasts then relay the bone to coincide with significantly less pressure on the tooth, thus manipulating of the orientation of the tooth. This article does not cite its references or sources. ... // Headline text The periodontal ligaments are considered part of the periodontium, as they are supporting tissue of a tooth. ... The alveolar process (processus alveolaris), also referred to as the alveolar bone, is the bone found in the jaws of a mouth containing the socket of teeth. ... An osteoblast (from the Greek words for bone and to build) is a mononucleate cell which produces a protein that produces osteoid. ...


Alternate use of term

An osteoclast can also be an instrument used to fracture and reset bones (the origin is Greek osteon:bone and klastos:broken). To avoid confusion, the cell was originally termed osotoclast. When the surgical instrument went out of use, the cell became known by its present name.


Notes

  1. ^ Netter, p. 169
  2. ^ Holtrop
  3. ^ Vaananen, p. 378
  4. ^ Netter, p. 169
  5. ^ Schoppet

References

  • Hankermeyer, C. R., et al. (2002), "Dissolution rates of carbonated hydroxyapatite in hydrochloric acid." Biomaterials, 23: 743-750, PMID 11771694
  • Holtrop, M. E. and G. J. King (1977), "The ultrastructure of the osteoclast and its functional implications." Clinical Orthopaedics and Related Research, 123: 177-196
  • Netter, Frank H. (1987), Musculoskeletal system: anatomy, physiology, and metabolic disorders. Summit, New Jersey: Ciba-Geigy Corporation
  • Schoppet M., et al. (2002), "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function." Arteriosclerosis, Thrombosis, and Vascular Biology, 22: 549-53, PMID 11950689
  • Vaananen, H. K., et al. (2000), "The cell biology of osteoclast function." Journal of Cell Science, 113: 377-381, PMID 10639325

External link

  • MedicineNet
  • MeSH Osteoclasts

  Results from FactBites:
 
Osteoclast definition - Medical Dictionary definitions of popular medical terms easily defined on MedTerms (282 words)
Osteoclast: A cell that nibbles at and breaks down bone and is responsible for bone resorption.
Osteoclasts are large multinucleate cells (cells with more than one nucleus) that differentiate from another type of cell called a macrophage.
In women, osteoclast activity is increased because of decreased estrogen after the menopause.
MUSC Children's Hospital - Research - Osteoclast Team (1162 words)
His research interests includes (i) Molecular aspects of osteoclast and osteoblast/stromal cell biology and gene regulation (ii) Osteopetrosis animal models, congenital bone fractures in spinal muscular atrophy; Paget's disease of bone and (iii) Cancer metastasis to bone.
At MUSC, in addition to osteoclast biological studies, his expertise in bone histochemistry has been resourceful to clinical trials for the treatment of osteopetrosis and juvenile osteoporosis.
Her current interests are osteoclast biology (mouse and human) focusing on culturing pure osteoclasts from the stem cells, investigating the dual role of cytokines and other biological modifiers on the function of normal and osteopetrotic/osteoporotic osteoclasts.
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