Introduction to gingival connective tissue
The connective tissue of the gingiva is termed as lamina propria. It is densely collagenous with a few elastic fibers. It consists of two layers: papillary and reticular layer. The papillary layer lies adjacent to the epithelium and the reticular layer is contiguous with the periosteum of the alveolar bone. In the papillary layer of connective tissue, papillary projections interdigitating with epithelial rete pegs can be seen. Densely packed collagen fibers can be seen in the connective tissue with specific orientations and attachments. Other important components of gingival connective tissue are various cells and macromolecules. Following is the detailed description of these components,
Gingival fibers:
There is a specific orientation and organization of the collagen fiber bundles in the gingival connective tissue, also referred to as fiber apparatus of the gingiva. These fiber bundles have been named according to their location, origin and insertion as dentogingival, alveologingival, dentoperiosteal, circular, semicircular, transgingival, intergingival, intercircular, transseptal and interpapillary groups 158-160.
Dentogingival fibers: These fibers are embedded in the cementum near the cementoenamel junction (CEJ) and fan out into the gingival connective tissue attaching gingiva to the teeth. On the facial and lingual surfaces of teeth, these fibers extend from the cementum outwards, in a fan like conformation.
Alveologingival fibers: These fibers extend from the periosteum of the alveolar crest into the gingival connective tissue. These fiber bundles attach the gingiva to the bone.
Dentoperiosteal fibers: These fibers extend laterally from the tooth to the periosteum of the alveolar bone. They attach the tooth to the bone.
Circular fibers: These fibers encircle the tooth in a ring-like manner coronal to the alveolar crest connecting adjacent teeth to one another. These fibers are not attached to the cementum of the tooth.
Semicircular fibers: The fibers emanate from cementum near the CEJ, cross the free marginal gingiva, and insert into a similar position on the opposite side of the tooth.
Transgingival fibers: These fibers extend from the cementum near the CEJ of teeth and run horizontally between adjacent teeth, linking them into a dental arch unit.
Intergingival fibers: These fibers extend in a mesiodistal direction along the entire dental arch and around the last molars in the arch. In this way, they link adjacent teeth into a dental arch unit.
Intercircular fibers: These fibers encircle several teeth in the arch linking adjacent teeth into a dental arch unit.
Transseptal fibers: These fibers pass from the cementum of one tooth, over the crest of alveolar bone to the cementum of the adjacent tooth. They connect adjacent teeth to one another and secure their alignment in the arch.
Interpapillary fibers: These fibers are located coronal to the transseptal fibers connecting the oral and vestibular interdental papillae of posterior teeth.
Cellular components of gingival connective tissue
There is a variety of resident cells in the gingival connective tissue, making around 8% of its total volume. Fibroblasts are the primary cellular element of the gingival connective tissue, responsible for the formation and degradation of the collagen fibers. They play an important role during healing after the periodontal surgery. Other cells, which can be seen in the gingival connective tissue are macrophages, mast cells, lymphoid cells and blood leukocytes. Following is the detailed description of the cellular components of gingival connective tissue,
Fibroblasts
Gingival fibroblasts are the most abundant cells in the periodontal connective tissue. They make around 65% of the total cell volume of the gingival connective tissue. According to their functional state, they exhibit considerable variation in their morphology, size, and shape. They are spindle-shaped or stellate-shaped cells (active fibroblasts) with centrally placed oval or round nucleus. These cells produce extracellular matrix products, i.e. collagen fibers and amorphous ground substance, thus playing an important role in the formation of extracellular matrix. Fibroblasts are also responsible for the resorption of collagen fibers, thus playing an important role in collagen homeostasis. Present evidence suggests a considerable heterogenecity in the fibroblast cell populations 161. When observed under an electron microscope, these cells demonstrate abundant mitochondria, a prominent Golgi apparatus and densely packed lamellae of rough endoplasmic reticulum, suggestive of active synthetic cells. The fibroblast activity is controlled by local cellular environment, both the extracellular matrix, and soluble factors.
Polymorphonuclear cells (PMN’s)
These are primary cells which are abundantly found in an acute inflammatory reaction. These cells are commonly found in the junctional epithelium where they travel along the chemoattractant gradient to reach the site of bacterial accumulation. Under the influence of various proinflammatory mediators, these cells migrate out of the blood vessels by trans-endothelial migration to reach the site of insult. Under healthy conditions when there is no inflammation, these cells are rarely found in the gingival connective tissue.
Lymphocytes and plasma cells:
Lymphocytes and plasma cells are the key cells involved in the immune response against infection. Most of the lymphocytes found in gingiva are T-lymphocytes, which are primarily present in the zone immediately adjacent to the junctional epithelium. These constitute the cell-mediated immune response against infection. The humoral response or the antibody-mediated response is generated through plasma cells, which are derived from mature B-cells. The mature B cells exhibit a ………….. Content available in the hard copy of the website…………. Content available in the hard copy of the website…..
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Monocytes and macrophages:
Monocytes and macrophages are mononuclear phagocytes that play an important role in tissue homeostasis and immunity. Monocytes circulate in the blood, bone marrow, and spleen and do not proliferate in a steady state. These cells possess chemokine receptors and pathogen recognition receptors that mediate their migration from blood to tissues during infection. Macrophages are resident phagocytic cells in lymphoid and non-lymphoid tissues. These cells are characterized by the presence of relatively small oval or indented nucleus, abundant cytoplasm containing primary and secondary lysosomes, microfilaments, scattered rough endoplasmic reticulum and numerous small vesicles distributed in the cytoplasm. Usually, only a small population of these cells is present in the normal non-inflamed gingiva. During inflammation, there is an increase in the number of these cells in the gingival connective tissue.
Mast cells:
Mast cells are large granular cells that arise from multipotent precursors in the bone marrow and are normally distributed throughout the connective tissues 162. These cells are involved in numerous activities ranging from control of vasculature to tissue injury and repair, allergic inflammation and host defense. These cells are located near blood vessels or nerve endings where they release their products on stimulation. Their products include heparin, histamine and large variety of other pro-inflammatory mediators, including interleukins IL-1, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-16, together with granulocyte-macrophage colony stimulating factor (GM-CSF), platelet-activating factor (PAF), RANTES, macrophage inflammatory protein (MIP-1a), and the arachidonic acid metabolites, prostaglandin E2 and leukotriene C4 163. It has been demonstrated that in inflamed and healing gingiva, the number of mast cells increases 164. The cell membrane of mast cells possesses a relatively large spectrum of receptors capable of mediating the interaction with components of the immune system, thus playing an important role in immune response. They are also an important source of growth factors, such as vascular endothelial growth factor or nerve growth factor.
Osteoblasts and osteoclasts:
These cells are found close to the alveolar process and are responsible for bone formation and resorption, respectively (described in alveolar bone). Cementoblasts and cementoclasts: These cells are responsible for the formation and resorption of cementum, respectively (described in alveolar bone).
Macromolecular components of gingival connective tissue:
The gingival connective tissue contains collagen and noncollagenous glycoproteins. The non-collagenous glycoproteins include laminin, fibronectin, proteoglycans, a small quantity of elastin and serum components.
Collagen:
It is the most abundant protein in the connective tissue and is involved in the formation of the structural framework of both hard and soft connective tissue. The characteristic feature of collagen is its balanced structure. Collagen molecules are synthesized by resident fibroblasts. To date, there are 28 known collagen types in mammals, which form triple helices through three polypeptide chains winding around each other in a rope-like structure 165, 166. The triple helical structure is formed due to the presence of glycine (Gly) at every third position in the amino acid chain. Hence, the collagenous domain has the repeated sequence X-Y-Gly [where X and Y can be any amino acid, but one of them is often a proline (Pro)]. All different forms of collagen cannot form fibrils. Those which can form fibrils include collagen Types I, II, III, V, XI, XXIV, and XXVII. In gingiva, the collagen accounts for 60% of the total tissue protein 167. Collagen Type I and Type III make the majority of the extractable collagen from gingival tissue accounting for around 99%. Collagen Type V accounts for less than 1% 168.
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Laminin:
Laminins are heterotrimeric proteins of the extracellular matrix that are composed of α-, β- and γ-subunits. There are multiple isoforms of each subunit yielding a variety (15) of laminin proteins cataloged to date. It binds to cell surface receptors as well as various matrix components. It is an important component of basal lamina due to its property to form fibrils and networks itself, as well as with collagen Type IV.
Fibronectin:
Fibronectin is a ubiquitous and essential component of the extracellular matrix (ECM). It is also an important component of plasma for its role in thrombosis. The name “fibronectin” is derived from the Latin words fibra, meaning fiber, and nectere, meaning to bind. Fibronectin is formed by the joining of two similar polypeptide subunits via a pair of disulphide bonds near the C-terminal of each subunit. It contains two major heparin-binding domains that interact with heparan sulfate proteoglycans. It also contains collagen as well as fibrin-binding sites. Cellular fibronectin is secreted by fibroblasts and multiple other cell types and is organized into fibrils contributing to the insoluble extracellular matrix. Fibronectin binds to many receptors of the integrin family. Along with this, it has a remarkably wide variety of functional activities. Besides binding to the cell surfaces through integrins, it also binds to a number of biologically important molecules that include heparin, collagen/gelatin, and fibrin. It plays an important role during wound healing. It facilitates spreading of platelets on the collagen fibers, their binding to fibrin clot, promoting opsonisation by phagocytic cells and promoting migration of fibroblasts. It has specific domains for binding proteoglycans, which make it an important binding material in the extracellular matrix.
Proteoglycans:
Proteoglycans are the proteins that are heavily glycosylated. Structurally, these are formed of glycosaminoglycans (GAGs) covalently attached to the core proteins. They constitute a major component of the extracellular matrix. An important function of proteoglycans in the extracellular matrix is to provide resilience and resistance to compression under pressure, which is due to their high degree of supramolecular organization.
The biosynthesis of proteoglycans require several modifying enzymes in addition to glycosyltransferases. These can be classified on the basis of the nature of their glycosaminoglycan chains. The protein part of the proteoglycans is synthesized by ribosomes and then it enters the lumen of the rough endoplasmic reticulum. The glycosylation of the proteoglycan occurs in the Golgi apparatus in multiple enzymatic steps. A tetrasaccharide link is then attached to a serine side chain on the core protein to serve as a primer for polysaccharide growth. Sugar units are then added to this structure in the presence of enzyme glycosyl transferase.
Table: Classification of proteoglycans based on the nature of their glycosaminoglycan chains
| Glycosaminoglycans | Small proteoglycans | Large proteoglycans |
|---|---|---|
| Chondroitin sulfate/Dermatan sulfate | Decorin, kDa=36, Biglycan, kDa=38 | Versican, kDa=260-370 |
| Heparan sulfate /chondroitin sulfate | Testican, kDa=44 | Perlecan, kDa=400-470 |
| Chondroitin sulfate | Bikunin, 25 kDa | Neurocan, kDa=136 Aggrecan, kDa=220 |
| Keratan sulfate | Fibromodulin, kDa=42, Lumican, kDa=38 |
The completely formed proteoglycans are then exported to extracellular matrix space by secretory vesicles. In gingival tissue, dermatan sulfate is the predominant glycosaminoglycan accounting up to 60% of the total. The remaining components include hyaluronic acid, heparan sulfate and chondroitin sulfate 188, 189. Initially, proteoglycans were considered as an inert cementing substance, but now it is clear that because of their charged nature, they are highly hydrated and are capable of interacting with a wide variety of matrix and cell surface components, which is vital for the maintenance of normal tissue function.
Elastin:
Elastin is another important structural protein found in the extracellular matrix (ECM) of gingival connective tissue. The elastin formation, also known as elastogenesis, takes place through the assembly and cross-linking of the protein tropoelastin. As discussed in the synthesis of collagen, the expression of genes encoding for elastin result in the formation of tropoelastin. The tropoelastin inside the cell, then associates with the elastin binding protein (EBP) and this complex is secreted out from the cell surface. The elastin binding protein (EBP) then dissociates from the tropoelastin molecule and re-enters the cell. The interchain covalent crosslinking system present in elastin is similar to that of collagen. Tropoelastin aggregates are oxidized by lysyloxidase leading to cross-linked elastin. Elastin plays a key structural role in elastic tissues, including arteries, skin, ligament, cartilage and tendons where it is found in high concentrations 190. It is also present in the connective tissue of oral mucosa and attached gingiva. A limited content of elastin is present in the periodontal ligament.
Conclusion
The gingival connective tissue is composed of cellular and extracellular components, both of which are very essential for the maintenance of homeostasis in the periodontal arena. In the above discussion, we studied various cellular and extra cellular components of the gingival connective tissue. With this basic knowledge now we can study other important components of the periodontium like periodontal ligament, cementum, and alveolar bone.
References
References are available in the hard copy of the website.
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