WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Malakar et al. World Journal of Pharmacy and Pharmaceutical Sciences SJIF Impact Factor 6.647 Volume 6, Issue 04, 212-228 Review Article ISSN 2278 – 4357
CELLS OF PERIODONTIUM
Dr. Maharshi Malakar*1, Dr. K.Rajapandian2, Dr.V.Kalaivani3, Dr. Y. Pradeep Kumar4, Dr. T.R. Aravindhan5 and Dr. Shanmugapriya R.6
Department of Periodontics.
Article Received on ABSTRACT 24 Jan 2017, The periodontium (peri = around, odontos = tooth) comprises the Revised on 14 Feb 2017, Accepted on 07 march 2017 following tissues the gingiva, the periodontal ligament, the root
DOI: 10.20959/wjpps201704-8846 cementum, and the alveolar bone.The periodontium, also called “the attachment apparatus” or “the supporting tissues of the teeth”, *Corresponding Author constitutes developmental, biologic, and functional unit which Dr. Maharshi Malakar undergoes certain changes with age and is, in addition, subjected to Department of morphologic changes related to functional alterations and alterations in Periodontics. the oral environment. There aredifferent type of cells present in periodontium. Those cells are morphologically different and have different function.
INTRODUCTION The periodontium (peri = around,odontos = tooth) comprises the following tissues the gingiva (G), the periodontal ligament(PL), the root cementum (RC), and the alveolar bone.[4] The alveolar bone consists of two components , the alveolar bone proper (ABP) and the alveolar process.[2] The periodontium, also called “the attachment apparatus” which undergoes certain changes with age and is, in addition, subjected to morphologic changes related to functional alterations and alterations in the oral environment.[4] Gingiva is the part of oral mucosa that covers the alveolar processes of the jaws and surrounds the necks of the teeth.[2] The periodontal ligament is the soft, richly vascular and cellular connective tissue which surrounds the roots of the teeth and joins the root cementum with the socket wall.[2] The cementum is a specialized mineralized tissue covering the root surfaces and occasionally, small portions of the crown of the teeth.[2] Alveolar Bone is a remarkably strong biologic construction material. The alveolar process (alveolar bone) is the thickened ridge of bone that contains the tooth sockets (dental alveoli) on bones that hold teeth. In humans, the tooth-bearing bones are the maxillae and the mandible.
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CELLS IN GINGIVA Cells in gingival epithelium: keratinocyte, non keratinocyte[2] Non keratinocyte cells are: Langerhans cells, Merkel cells, melanocytes. Cells in gingival connective tissue: Fibroblast, Mast cells, Inflammatory cells.[2]
CELLS IN GINGIVAL EPITHELIUM KERATINOCYTE The principal cell type of gingival epithelium –is the keratinocyte. Keratinocyte make up 90% of the gingival cell population. Keratinocytes are the only cells which contains melanosomes in periodontium.[2]
Origin Keratinocytes origin from ectodermal germ layer.[3]
Proliferation Proliferation of keratinocytes takes place by mitosis in basal layer and less frequently in suprabasal layers-a small proportion remain as a proliferative compartment while a layer number migrate to the surface.[2]
Differentiation This involves the process of keratinization-which consists of a space of biochemical and morphological events that occur in the cells as it travels from the basal layer to the surface.[2]
The changes are Progressive flattening of the cells Increasing prevalence of to no filaments and intercellular junctions coupled to the production of keratohyaline granules. Disappearance of the nucleus.[2]
A complete keratinization process leads to the production of an orthokeratinized superficial horny layer similar to that of the skin with no nuclei in the stratum corneum and a well- defined stratum granulosum. Only some areas of the outer gingival epithelium are orthokeratinized; the other gingival areas are covered by parakeratinized or nonkeratinized epithelium.[2]
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STRUCTURE Electron microscopy reveals that keratinocytes are interconnected by structures on the cell periphery called desmosomes. These desmosomes have a typical structure consisting of two dense attachment plaques into which tonofibrils insert and an intermediate, electron-dense line in the extracellular compartment. Tonofilaments, which are the morphologic expression of the cytoskeleton of keratin proteins, radiate in brush like fashion from the attachment plaques into the cytoplasm of the cells. The space between the cells shows cytoplasmic projections resembling microvilli that extend into the intercellular space and often interdigitate. Cytoplasmic organelle concentration varies among different epithelial strata. Mitochondria are more numerous in deeper strata and decrease toward the surface of the cell.[3]
FUNCTION Wounds to the skin will be repaired in part by the migration of keratinocytes to fill in the gap created by wound.This cell is a barrier against environmental damage..This can produce pro inflammatory mediators such chemokines.[3]
NONKERATINOCYTES These are the cells do not contain the large number of tonofilaments and desmosomes seen in epithelial keratinocytes,and none participates in the process of maturation seen in oral epithelia, there fore, they often called collectively nonkeratinocytes.[4]
MELANOCYTE Melanocytes are dendritic cells located in the basal and spinouts layers of gingival epithelium.[8]
Origin Melanocytes arise embryologically from the neural crest ectoderm and enter the epithelium at about 11 weeks of gestation.[3]
STRUCTURE Melanocytes lack desmosomes and tonofilaments but possess long dendritic processes that extend between the keratinocytes,often passing through several layers of cells.Melanin is synthesized within the melanocytes as small structures called pre melanosomes or melanosomes,which are inoculated into the cytoplasmof adjacent keratinocytes by the
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dendritic process of melanocytes.Group of melanosomes often can be identified under the light microscope in sections of heavily pigmented tissue stained with hematoxyllin and eosin. These groups referred as melanin granules.These melanosomes contain tyrosinase which hydroxylates tyrosine to dehydroxyphenylalanine (dopa),which in turn is progressively converted to melanin. Melanin granules are phagocytosed and contained within other cells of epithelium and connective tissue called-melanophages or melanophores4.
FUNCTION Produce melanin pigmentation in gingiva. Prevent gingiva from environmental factors such as uv ray.[8]
LANGERHANS CELLS These are the dendritic cells located among keratinocytes at all supra basal levels.[2]
ORIGIN They belong to mononuclear phagocyte system as modified monocytes derived from bone.2
STRUCTURE This cells lacks desmosomal attachments to surrounding cells and therefore appears as a clear cell in histologic sections. The langerhans cell is characterized ultrastructurally by a small rod or flask shaped granule, sometimes called the birbeck granule. They are found in oral epithelium and in smaller numbers in sulcular epithelium and are probably absent in junction epithelium-bouchard.[2]
FUNCTION Evidence suggest that langerhans cells have an immunological function,recognizing and processing antigenic material that enters the epithelium from the external environment and presenting it to t lymphocytes[3]
MERKEL CELL Merkel cells also known as merkel ranvier cells are oval shaped cells located in the deeper layers of the epithelium[3]
ORIGIN They are derived from neural crest.[2]
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STRUCTURE Merkel cells are located in the deeper layers of the epithelium, harbor nerve endings, and are connected to adjacent cells by desmosomes. They have been identifiedas tactile perceptors. The epithelium is joined to the underlying connective tissue by a basal lamina 300 to 400 A thick, lying approximately 400 A beneath the epithelial basal layer. The basal lamina consists of lamina lucida and lamina densa. Hemidesmosomes of the basal epithelial cells about the lamina lucida, which is mainly composed of the glycoprotein laminin. The lamina densa is composed of type IV collagen. The basal lamina, clearly distinguishable at the ultrastructural level, is connected to a reticular condensation of the underlying connective tissue fibrils (mainly collagen type IV) by the anchoring fibrils-moss .The complex of basal lamina and fibrils if periodic acid Schiff positive and agrophillic line are observed at the optical level. The basal lamina is permeable to fluids but act as a barrier to particulate matter.[3]
FUNCTION Merkel cell contain dense core granules, thus they have neuroendocrine function. This cell act as a mechanoreceptor.[4]
Cells in gingival connective tissue FIBROBLAST These are the preporderent cellular element.they are widely distributed between the gingival fibers and is found in perivascular locations. The fibroblasts are typically stellate shaped and have extensive processes that are joined by intercellular junctions to the processes of the other fibroblasts.[3]
Origin Gingival connective tissue fibroblasts develop from perifollicular mesenchyme, a derivative of the stomodeal mesoderm.[3]
Structure Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibrocytes are smaller, spindle shaped, and have a reduced rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Gingival fibroblasts show considerable variation in morphologic development, from highly robust cells containing
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an abundance of rough endoplasmic reticulum, well-developed Golgi complexes, and mitochondria to fibroblasts that show signs of swelling and degeneration. Such changes probably reflect site-to-site variations in cytokines and other biologic mediators of inflammation. Within inflamed gingival connective tissue, plasma cells are found in clusters and/or in close contact with fibroblasts.[3]
FUNCTIONS Gingival fibroblasts perform several functions beyond matrix deposition. They secrete collagenase and are active in matrix deqradatlon. During normal development of the periodontium, gingival fibroblasts do not come into contact with the tooth surface. In general, gingival connective tissues have a high potent ial for regeneration. The collagen of gingival connective tissue turns over more rapidly than that of skin and bone but more slowly than that of the periodontal ligament.[3]
DIFERENCE BETWEEN GINGIVAL AND PERIODONTAL FIBROBLAST GINGIVAL FIBROBLAST PERIODONTAL FIBROBLAST Fibroblasts of the periodontal ligament Gingival connective tissue fibroblasts originate from the dental develop from perifollicular mesenchyme, a follicle (sac), a derivative of the neural crest derivative of the stomodeal mesoderm. ecto mesenchyme. The fibroblasts of the periodontal ligament During normal development of the become juxtaposed to the tooth surface soon periodontium, gingival fibroblasts do not after the disruption of the root sheath. They come into contact with the tooth surface. have the capacity to fabricate an attachment matrix (acellular cementum). Pdl fibroblast have less potential for gingival connective tissues FIBROBLAST regeneration compare to gingival have a high potential for regeneration fibroblast Gingival fibroblast have less proliferative Pdl fibroblast have greater proliferative rate. rate.
MAST CELLS Mast cell (also known as a mastocyte or a labrocyte is a type of white blood cell.[4]
ORIGIN Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuro immune systems and contains many granules rich in histamine and heparin.[4]
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STRUCTURE Mast cells were first described by Paul Ehrlich in his 1878 doctoral thesis on the basis of their unique staining characteristics and large granules. These granules also led him to the incorrect belief that they existed to nourish the surrounding tissue, so he named them Mastzellen (from German Mast, meaning "fattening", as of animals).Mast cells are generally located perivascularly and are seen rarely within the epithelium. These cells are relatively small, round or oval cell having a diameter of about 12-15um.The cells are characterized by numerous cytoplasmic granules, which frequently obscure the small round nucleus. The granules stain with basic dyes are most readily demonstrated by virtue of their capacity to stain metachromatically with dyes such as azure. They are positively stained by pas reaction. Electron microscopy shows the mast cell cytoplasm to contain free ribosomes, granular err, Few round mitochondria and a prominent Golgi apparatus. the granules average 0.5-1 um in diameter and are membrane bound.[3]
Function The cytoplasmic granules contains histamine which mediates the early stages of inflammation. They also produce heparin which may modulate the rate of bone resorption. Mast cells prevent parasitic infections through ige signaling.[3]
INFLAMMATORY CELLS In clinically normal gingiva, small foci of plasma cells and lymphocytes are found in the connective tissue near the base of the sulcus. Neutrophils can be seen in relatively high numbers in both the gingival connective tissue and the sulcus. These inflammatory cells usually are present in small amounts in clinically normal gingiva. Speculations about whether small amounts of leukocytes should be considered a normal component of the gingiva or an incipient inflammatory infiltrate without clinical expression are of theoretic rather than practical importance. Lymphocytes are absent when gingival normalcy is judged by very strict clinical criteria or under very special experimental conditions8, 80 but are practically constant in healthy normal gingiva, even before complete tooth eruption. Immuno histochemical studies using monoclonal antibodies have identified the different lymphocyte subpopulations.[3] The infiltrate in the area below the junctional epithelium of healthy gingiva in recently erupted teeth in children is mainly composed of T-lymphocytes (helper, cytotoxic, suppressor and natural killer) and thus could be interpreted as a normal lymphoid tissue involved in the early defense recognition system. As time elapses, B-lymphocytes and plasma
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cells appear in greater proportions to elaborate specific antibodies against already recognized antigens that are always present in the sulcus of clinically normal gingiva. Neutrophils can be seen in relatively high numbers in both the gingival connective tissue and the sulcus. These inflammatory cells usually are present in small amounts in clinically normal gingiva. The neutrophilic granulocytes, also called polymorphonuclear leukocytes, have a characteristic appearand. The nucleus is lobulate and numerous lysosomes (L), containing lysosomal enzymes, are found in the cytoplasm. The lymphocytes are characterized by an oval to spherical nucleus containing localized areas of electron-dense chromatin. The narrow border of cytoplasm surrounding the nucleus contains numerous free ribosomes, a few mitochondria (M), and, in localized areas, endoplasmic reticulum with fi xed ribosomes.[3]
CELLS IN PERIODONTAL LIGAMENT Cells in periodontal ligament are FIBROBLAST Fibroblasts are the most abundant cells in the PDL. The fibroblastic cell type and its products, the molecules of the extracellular matrix, are among the oldest and most conserved structures of multi cellular organisms. Not all fibroblasts are exactly alike3 .
ORIGIN PDL fibroblasts have a neural crest origin.[3]
Structure Synthetic activity and adhesive interaction with the surrounding extracellular matrix determine the shape of a fibroblast. Progenitor fibroblasts are smaller, less polarized, and contain less rough endoplasmic reticulum (RER) and fewer Golgi saccules.[3] When grown in vitro on flat surfaces, fibroblasts in nonconfluent cultures assume a well-spread, flattened shape, presenting a triangular profile when viewed from above. Cytoplasmic polarity is evident; the nucleus is located in the narrow end and the Golgi complex faces the broad end of the cell. In three-dimensional matrices such as collagen gels, or in connective tissues in vivo, the fibroblast assumes a more complex shape, reflecting its contact with a matrix substratum on many of its surfaces. Numerous cell processes extend into the spaces between collagen fiber bundles. Macula adherens and gap junctions are made between the cell processes of neighboring fibroblasts. Synthetically active fibroblasts are larger, more elongated, and more polarized than are inactive fibroblasts. Most PDL fibroblasts are highly active cells, exhibiting an elongated, well-polarized cytoplasm with extensive areas of contact
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to collagen fibers. Exceptions are noted around blood vessels and near the surface of the cementum, where fibroblast-like cells appear smaller and less active. Most fibroblasts in the PDL contain large amounts of RER and well developed Golgi complexes, indicative of a high rate of protein synthesis. The Golgi complex of the PDL fibroblast contains several Golg I stacks, composed of cisternae and terminal saccules. Each Golgi stack is made up of five cisternae, about 2 urn in length, term inating at each end in an expanded saccule. Immature cisternae at the cissurface of the Golgi complex are slightly dilated and in routine preparations devoid of any stainable content. The saccules associated with these cisternae contain fine, loosely arranged filaments. Coated vesicles are routinely seen in association with the surface of these saccules, suggesting that they are condensing vacuoles. The cisternae of the transsurface contain dense material, and their associated saccules contain rodlike structures with globular terminal elements, resembling segment longspacing collagen aggregates. These saccules are released to form pre secretory granules that quickly associate to microtubules. Auto radiographic studies of the incorporation and secretion of tritiated amino acids, such as proline and glycine, as well as biochemical studies, have confirmed a high rate of protein secretion in the PDL.[3]
Functions The fibroblast is not only responsible for the formation of collagen fiber networks but is also involved in the removal of collagen fibrils. Periodontal ligament fibroblasts are also needed to maintain the normal width of the PDL by preventing the encroachment of bone and cementum into the PDL space. In vitro studies have demonstrated that fibroblasts are eminently capable of phagocytosing collagen fibrils from the extracellular environment and degrading them inside phagolysomal bodies. In vitro studies of PDL fibroblasts have shown a positive correlation between cellular aging and collagen phagocytosis.[3]
Monocytes and macrophages Cells of the monocyte and macrophage lineage are normal inhabitants of the PDL. These cells are typically found in the perivascular and peri neural cuffs of loose connective tissue and are rarely observed to reside in the dense connective tissue of the principal fiber bundles.[3]
ORIGIN This cell derived from monoblasts and macrophage derived from multipotent cells of bone marrow known as hematopietic stem cells.[3]
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Structure In light microscopic sections, monocytes and macrophages appear round to oval in outline and are characterized by a finely ruffled surface. At the ultra structural level, the monocyte cell surface is observed to have many microvilli and folds and to give rise to many coated vesicles. Dense lysosomal granules are characteristic features of the cytoplasm. Activated monocytes contain a larger Golgi complex, more RER, a more highly ruffled cell surface, and cytoplasmic polarity. Macrophages, arising by the maturation of activated monocytes, are typically larger and contain numerous phago lysosomal inclusions. Monocytes exit blood vessels to enter the PDL in response to chemotactic stimuli.[3]
Function: During inflammation of the PdL, 1L-1 f3 and tumor necrosis factor ex contribute to monocyte infiltration by stimulating fibroblasts to secrete macrophage chemoattractant protein. Numerous substances, including endotoxin, immune complexes, and Iymphokines, can activate monocytes. Activated monocytes secrete collagenase, elastase, plasminogen activator (PA), and lysosomal hydrolases and are thus highly capable of degrading extracellular matrices.Macrophage plays an important role in wound healing. Macrophage play a key role in removing dead cells And cellular debris.This cells have a crucial role in regulating immune response.3
The epithelial rests of Malassez Epithelial cell rests of Malassez (ERM) are integrated in the periodontal ligament .Epithelial cell rests of Malassez were first described by Augustin Serres.[3]
ORIGIN Epithelial cell rests of Malassez originate from the degeneration of Hertwig’s epithelial root sheath to form quiescent cell rests that persist as the sole epithelial cells in the periodontium.[2]
STRUCTURE Louis-Charles Malassez provided a full description of their morphology and distribution in 1884 and noted that these epithelial cells persist to form part of the adult periodontal ligament. Due to the numerous physiological and regenerative functions that ERM perform within the periodontal ligament, the authors suggest that the current nomenclature of epithelial cell “rests” should be replaced by the term epithelial “network” in order to emphasize the central role that these cells play in the homeostasis of the tooth supporting
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apparatus[3]. Form a latticework in the periodontal ligament and appear as either isolated clusters of cells or interlacing strands depending on the plane in which the microscopic section is cut. Continuity with the junctional epithelium in experimental animals has been suggested. The epithelial rests are considered remnants of Hertwig's root sheath, which disintegrates during root development. Epithelial cell rests are distributed close to the cementum throughout the periodontal ligament of most teeth and are most numerous in the apical and cervical areas. They diminish in number with age by degenerating and disappearing or undergoing calcification to become cementicles. The cells are surrounded by a distinct basal lamina, are interconnected by hemidesmosomes, and contain tonofilaments. Epithelial rests proliferate when stimulated and participate in the formation of periapical cysts and lateral root cysts.[2]
FUNCTION We also highlight the capacity of ERM to undergo epithelial mesenchymal transitions, which indicates their involvement in periodontal regeneration. More recent experiments have elucidated their functional role in maintaining constant the width of the periodontal ligament and their additional role in the regeneration of periodontal tissues. Characterization of the cytokine profile of ERM have brought to light important bone resorbing factors, growth factors, chemokines and related proteins which are directly implicated in the process of bone remodelling.ERM in the periodontal ligament involves paracrine signalling to the surrounding alveolar bone.[4]
CELLS IN ROOT CEMENTUM CEMENTOBLAST A cementoblast is a biological cell that forms from the follicular cells around the root of a tooth, and whose biological function is cementogenesis, which is the formation of cementum (hard tissue that covers the tooth root). The mechanism of differentiation of the cementoblasts is controversial but circumstantial evidence suggests that an epithelium or epithelial component may cause dental sac cells to differentiate into cementoblasts, characterised by an increase in length. Other theories involve Hertwig epithelial root sheath (HERS) being involved.[4]
ORIGIN Cementogenesis is the formation of cementum, one of the three mineralized substances of a tooth. Cementum covers the roots of teeth and serves to anchor gingival and periodontal
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fibers of the periodontal ligament by way of Sharpey fibers to the alveolar bone (some types of cementum may also form on the surface of the enamel of the crown at the cementoenamel [3] junction {CEJ}).
STRUCTURE The initially formed cementum in coronal two-thirds of the root is acellular, but when the cementoblasts get trapped in lacunae in their own matrix like bone cells (see further discussion below), the cementum is called cellular or secondary cementum and is present only in the apical third of the root. Thus cementoblasts resemble bone-forming osteoblasts but differ functionally and histologically. The cells of cementum are the entrapped cementoblasts, the cementocytes. Each cementocyte lies in its lacuna (plural, lacunae), similar to the pattern noted in bone. These lacunae also have canaliculi or canals. However, these canals in cementum do not contain nerves, nor do they radiate outward. Instead, the canals are oriented toward the periodontal ligament (PDL) and contain cementocytic processes that exist to diffuse nutrients from the ligament because it is vascularized. The progenitor cells also found in the PDL region contribute to the mineralization of the tissue. Once in this situation, the cementoblasts lose their secretory activity and become cementocytes. However, a layer of cementoblasts is always present along the outer covering of the PDL.[4]
FUNCTION Cementoblasts lay down the organic matrix of cementum called cementoid which later gets mineralized by minerals from oral fluids. Thus the cementoblasts lay down collagen and secrete osteocalcin and sialoprotein. Osteocalcin and sialoprotein are bone morphogenetic proteins (also known as BMPs) that are often linked to the development and mineralization of periodontal tissues. They possess all the organelles associated with protein synthesis such as RER and Golgi apparatus. More specifically, bone morphogenetic protein-2 (BMP-2) acts on the cementoblasts in the periodontal tissue. The effect of BMP-2 on cementoblasts reduces gene expression of collagen and mineralization.[4]
ALVEOLAR BONE TYPES OF CELLS Pre osteoblasts, osteoblasts, osteocytes, bone-lining cells.osteoclast.
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PREOSTEOBLAST Periosteal and connective tissue pre-osteoblasts have the morphologic appearance of an inactive fibro-blast, containing many free ribosomes, only a few profiles of rough endoplasmic reticulum (RER), and a small Golgi complex. During differentiation, preosteoblasts make contact with adjacent preosteoblasts or with previously differentiated osteoblasts, develop cytoplasmic polarity, and greatly increase the amount of RER and Golgi cisternae.Mesenchymal cell differentiation into the osteogenic cell line is preceded by the activation of the Osf2/Cbfa 1 gene, which appears to serve as a master gene to turn on the expression of osteocalcin, osteopontin, bone sialoprotein, and collagen synthesis. The Osf2jCbfa1 protein is induced by bone morphogenetic protein 7 and is decreased by vitamin D3. Experimental studies have detected high levels of Osf2jCbfa1 expression in the developing mandible and maxilla as well as in tooth buds .Mutations in Osf2/Cbfa 1 block bone matrix formation and cause cleidocranial dysplasia, an autosomal dominant disease characterized by a variety of skeletal abnormalities, including short stature, poorly developed clavicles, and supernumerary teeth.[3]
OSTEOBLAST This are the cells with a single nucleus that synthesize bone.[3]
ORIGIN Osteoblasts arise from mesenchymal stem cells.[3]
STRUCTURE In well-preserved bone studied at high magnification via electron microscopy, individual osteoblasts are shown to be connected by tight junctions, which prevent extracellular fluid passage and thus create a bone compartment separate from the general extracellular fluid. The osteoblasts are also connected by gap junctions, small pores that connect osteoblasts, allowing the cells in one cohort to function as a unit. The gap junctions also connect deeper layers of cells to the surface layer (osteocytes when surrounded by bone). Hematoxylin and eosin staining (H&E) shows that the cytoplasm of active osteoblasts is slightly basophilic due to the substantial presence of rough endoplasmic reticulum. The active osteoblast produces substantial collagen type I. About 10% of the bone matrix is collagen with the balance mineral. The osteoblast's nucleus is spherical and large. An active osteoblast is characterized morphologically by a prominent Golgi apparatus that appears histologically as a clear zone adjacent to the nucleus. The products of the cell are mostly for transport into the osteoid, the
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non-mineralized matrix. Active osteoblasts can be labeled by antibodies to Type-I collagen, or using naphthol phosphate and the diazonium dye fast blue to demonstrate alkaline phosphatase enzyme activity directly.[3]
FUNCTION Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells. They synthesize dense, crosslinked collagen and specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which compose the organic matrix of bone.In organized groups of connected cells, osteoblasts produce hydroxyapatite that is deposited, in a highly regulated manner, into the organic matrix forming a strong and dense mineralized tissue - the mineralized matrix. It is an important store of minerals for physiological homeostasis including both acid-base balance and calcium or phosphate maintenance.[3]
OSTEOCYTE An osteocytes, a star-shaped type of bone cell, is the most commonly found cell in mature bone tissue, and can live as long as the organism itself. HALF LIFE: Osteocytes have an average half life of 25 years, ORIGIN: osteocytes develop in mesenchymal. They are derived from osteoprogenitor.
STRUCTURE Osteocytes have a stellate shape, approximately 7 micrometers deep and wide by 15 micrometers in length. The cell body varies in size from 5-20 micrometers in diameter and contain 40-60 cell processes per cell, with a cell to cell distance between 20-30 micrometers. A mature osteocytes contains a single nucleus that is located toward the vascular side and has one or two nucleoli and a membrane. The cell also exhibits a reduced size endoplasmic reticulum, Golgi apparatus and mitochondria, and cell processes that radiate towards the mineralizing matrix. Osteocytes form an extensive connecting syncitial network via small cytoplasmic/dendritic processes in canaliculi.[3]
FUNCTION Although osteocytes are relatively inert cells, they are capable of molecular synthesis and modification, as well as transmission of signals over long distances, in a way similar to the nervous system Osteocytes are thought to be mechanosensor cells that control the activity of osteoblasts and osteoclasts within a basic multicellular unit (BMU), a temporary anatomic
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structure where bone remodeling occurs.Osteocytes generate an inhibitory signal that is passed through their cell processes to osteoblasts for recruitment to enable bone formation. The osteocyte is an important regulator of bone mass and a key endocrine regulator of phosphate metabolism. Osteocytes synthesize sclerostin, a secreted protein that inhibits bone formation by binding to LRP5/LRP6 coreceptors.[3]
Bone-lining cells Bone-lining cells extend flat cytoplasmic sheets over the bone surface.It is estimated that 80% of the total bone surface is covered by bone-lining cells. Approximately 20 bone-lining cells line every linear millimeter of resting bone surface. Beneath the bone-lining cell, the osteoid is replaced by a narrow zone of unmineralized connective tissue matrix.[3]
ORIGIN This cell derived from embryo mesenchyme.[3]
STRUCTURE Bone-lining cells contain a relatively small number of organelles. Mitochondria, free ribosomes, RER, and Golgi cisternae are located adjacent to the flattened nucleus of the bone-lining cell. Bone-lining cells are not connected by zonula occludens junctions; thus there is no tight cytoplasmic barrier between bone and the general body fluids. Despite the lack of occluding junctions, differences in ionic composition exist between bone fluid and the interstitial fluids. Differential ion concentrations between these two compartments are thought to be maintained by a combination of cell membrane transport and charge restriction mediated by fixed proteo glycansin the lamina limitans.[3,9]
FUNCTION Bone-lining cells act as gatekeepers, protecting the bone surface from osteoclasts, regulating the ionic composition of bone fluid, and regulating the initiation of new bone formation.Bone-lining cells can be stimulated to incorporate thymidine, divide and rise to osteoblasts. The osteoprogenitor capacity of bone-lining cells is important in responding to increased strain and in forming a fracture callus during bone repair.[3,9]
Osteoclast An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodelling of bones of the vertebral skeleton. The osteoclast
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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. This process also helps regulate the level of blood calcium.[4]
Development Since their discovery in 1873 there has been considerable debate about their origin. 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. After years of controversy it is now clear that these cells develop from the self fusion of macrophages. It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) 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. osteoclasts are derived from the hematopoietic lineage.[4]
Structure An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are about 150-200 µm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. 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. The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone.[7]
FUNCTION Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in a small cavity called Howship's lacunae, formed from the digestion of the underlying bone. The sealing zone is the attachment of the osteoclast's plasma membrane to the underlying bone. Sealing zones are bounded by belts of specialized 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 through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled border into the resorptive cavity,
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acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. 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.[7]
CONCLUSION There are various types of cells present in periodontium. those cells are morphologically and functionally differ from each other. Those cells play an important role to maintain the function, structure of periodontium. Although these cells help to protect periodontium from environmental hazards.
REFERENCES 1. TEN CATES oral histology, 325-329 2. CARRANZA'S Clinical PERIODONTOLOGY 9th edition, 19-45 3. Oral cells and tissue-R.R.GARANT DMD, 123-195 4. CLINICAL PERIODONTOLOGY JAN LINDHE 5. CELLS OF PERIODONTIUM A.H.MELCHER.PERIODONTAL 2000,1993 OCT 39-38 6. TISSUES AND CELLS OF THE PERIODONTIUM, THOMAS M.HASSELL, OCT 1993; 9-38, PERIODONTAL 2000 7. MOLECULAR BIOLOGY OF PERIODONTIUM BY Arun kv 8. ELECTRON MICROSCOPY OF MELANOCYTES;M.S.BRICK, FEB 1963 9. 1989 Sep; 3(3): 953-60; discussion 960-1.Bone lining cells: structure and function. Miller SC1, de Saint-Georges L, Bowman BM, Jee WS.PUBMED 10. Pesqui Odontol Bras, Oct-Dec 2002; 16(4): 319-25. Epub 2003 Feb 12.[Comparison between gingival and periodontal ligament fibroblasts from the same subject].
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