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Year : 2019  |  Volume : 10  |  Issue : 3  |  Page : 149-153

Role of collagen in oral and systemic diseases

1 Department of Oral Pathology and Microbiology, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Oral Pathology and Microbiology, Yogita Dental College and Hospital, Ratnagiri, Maharashtra, India

Date of Submission11-Jun-2019
Date of Acceptance24-Jul-2019
Date of Web Publication15-Oct-2019

Correspondence Address:
Dr. Amol Jain
5/130, Vikas Khand, Gomtinagar, Lucknow - 226 010, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/srmjrds.srmjrds_43_19

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Collagen has been studied appreciably by a massive variety of researchers since 20th century. It is the most important fibrous glycoprotein among the ground substances and forms the core component within the connective tissue structures such as tendons, cartilage, the organic matrix of bone, and cornea, and they retain the muscularity and firmness of these elements. It has triple helices architecture. The collagen family so far has identified 20 different forms. All types of collagens play a role by synthesizing fibers and network of microfibers present in the ground substance, basal lamina also remaining constituents of the matrix. In this review we discuss about the organisation and role of different collagen forms in various tissues. It presents the fundamental structure, synthesis and the different disorders or syndromes which occur due to the defects in the collagen biosynthesis.

Keywords: Collagen, collagen biosynthesis, oral submucous fibrosis, osteogenesis imperfecta, Stickler syndrome

How to cite this article:
Jain A, Chandurkar K, Jaiswal R. Role of collagen in oral and systemic diseases. SRM J Res Dent Sci 2019;10:149-53

How to cite this URL:
Jain A, Chandurkar K, Jaiswal R. Role of collagen in oral and systemic diseases. SRM J Res Dent Sci [serial online] 2019 [cited 2023 May 28];10:149-53. Available from:

  Introduction Top

The word “collagen” is derived from Greek term “kola” meaning “glue” and suffix “gen” denoting “producing.” Collagen disintegrates and forms soluble protein, i.e., gelatine or animal glue when warmed in water. Collagen, the most basic protein, was found in the connective tissue of the petrified bones of Tyrannosaurusrex remnants aged around 68 million years.[1] The cardinal role of the ground substance present extracellularly provides them support structurally and biochemically.[2] To maintain the structural integrity and functionability of vital tissues, a group of proteins are present which provide strength, resilience, and rigidness.[3] Collagen constitutes variety of proteins creating a triple helical structure made up of three series of amino acids, and the extramolecular forms preset in the ground substance are formed from different types of collagen proteins in spite of their proportion, purpose, and tissue allocation differ markedly. These structures are essential for cellular functions such as adherence and extracellular matrix activation and for synthetic functions such as hydroxylation of collagen's Lys and Pro sediments. The chief configuration of the collagen molecule was identified as(Gly-X-Y)(n). The framework is often denoted by the Gly-Pro-Hyp tripeptide. Glycine, one of the major components of the matrix, forms almost one-third of the structure among the residues of the amino acids. Different types of collagen contribute performing various functions [Table 1]. Major collagen protein formed around different structures is almost 90% Type I collagen.[4]
Table 1: Collagen types and their functions

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  Structure of Collagen Top

Collagen (COL) is the major architectural protein in all mammals. In Homo sapiens, it consists of one-third of the whole proteins. However, 28 distinct types of collagen have been identified, which comprise 46 different polypeptide chains[2] consisting of three helix linear coiled molecules in the form of chains being amino acid their main component. The amino acids constituting in collagen are glycine, proline, and hydroxyproline. Difference in collagen types is in their arrangement of the molecules, length, and interruption in the helix and termination ends of helix domain. It comprises three parallel helixes on the right and polyproline Type II helices on the left of the structural unit. The molecule of collagen is made up of Gly-Pro-Hyp tripeptide.[4] The unstained collagen fibers of connective tissue are usually <10 μm in diameter and appear colorless. They appear as long, wavy, pink fiber bundles after staining with hematoxylin and eosin. Electron micrographs of collagen fibers stained with heavy metals display crossbanding at regular intervals of 67 nm, a characteristic property of these fibers. These fibers are formed from parallel aggregates of thinner fibrils of 10–300 nm in diameter.[3]

  Classification Top

  1. Ehlers–Danlos syndrome (EDS)
  2. Osteogenesis imperfecta
  3. Stickler syndrome
  4. Alport syndrome
  5. Marfan syndrome
  6. Epidermolysis bullosa
  7. Systemic sclerosis
  8. Oral submucous fibrosis
  9. Scurvy
  10. Lupus erythematosus (LE).

Ehlers–Danlos syndrome

EDS consists of a divergent group of hereditary connective tissue disorder, featured by hypermobility of joints, skin hyperextensibility, and tissue fragility.[5] Defects during collagen synthesis in various mesenchymal tissues such as skin, blood vessels, muscles, tendons, joints, and visceral organs exhibit an increase in their elasticity.[6] Its etiology is determined by polygenes where the most common pattern is autosomal dominant; however, a few X-linked recessive and other recessive factors are also recognized.[7] The chief established processes causing EDS are factors such as insufficiency of collagen-producing catalysts, governing adverse outcomes of abnormal collagen α-chains, and Haploinsufficiency adequacy. Majorly patients suffer from the defect associated with collagen Type V alpha-1 chain and collagen Type V alpha-2 chain alleles due to their overpowering adverse effects. Whereas, studies show that haploinsufficiency of COL5A1 is seen more frequent.[8] The typical symptoms are hyper mobility of joints, increased elasticity of skin. The skin is characterized with features such as thin, friable, ecchymosis, hematomas, uncontrolled bleeding and dystrophic scars.[9]

Osteogenesis imperfecta

Osteogenesis imperfecta is an inherited systemic disorder associated with Type I collagen protein. Major tissues involved are sclera, ligaments, bone, and dentin. This disorder is responsible for varying degrees of bone frailty and low bone mass which lead to increased proneness to fracture. Various synonyms have been used so far such as brittle bone disease, Lobstein disease, glass bone disease, Vrolik's syndrome, and Porak and Durante's disease.[10] Associated skeletal and oral symptoms include maxillary hypoplasia, ectopic teeth, large forehead, frontal and temporal bossing, and dentinogenesis imperfecta.[11] The pathogenesis is associated with a point mutation of glycine residue in COL1A1 on 17q21 or COL1A2 on 7q22.1 which encodes α-1 and α-2 chains for Type I collagen. These mutations lead to the formation of abnormal collagen qualitatively and quantitatively where immature collagen (procollagen) is not transforming to mature collagen (Type I). The involvement of α-1 or α-2 chains results in varying degrees of defect from mild to severe. When a premature stop codon is formed within COL1A1, its most likely outcome is osteogenesis imperfecta Type I. The products formed during the alteration in crosslinking of genes are unstable and eliminated by process called nonsense-mediated decay. Osteoblasts facilitating altered Type I collagen gene may have an atypical expression pattern of additional proteins present in the matrix such as fibronectin, proteoglycan, thrombospondin, and hyaluronan.[12]

Stickler syndrome

Also known as hereditary progressive arthro-ophthalmodystrophy, is heterozygous, autosomal dominant mesenchymal tissue condition altogether with the involovement of ocular, craniofacial, and musculoskeletal systems. The characteristic features are flat mid-face, near sightedness (myopia), tearing up of the lining of eyes (retinal detachment), clouding in lens of eyes (cataracts), hearing loss, joint diseases (arthropathy), and cleft palate (or bifid uvula) and musculoskeletal abnormalities. Patients exhibiting cleft palate or acute ophthalmic findings or a positive family history are acknowledged mostly in childhood. Patients generally appear tall and with lean gait. The defect in chromosomes has distinct phenotypic illustration.[13] Eventually, mutations recognized are associated with collagen Type II alpha-1 chain detected on chromosome 12q13.11-p13.2, guiding to a premature nonsense trinucleotide sequence. Sometimes, patients exhibit a fibrillar Type II vitreous phenotype also in association with genetic alteration by pair substitution in COL11A1 gene responsible for synthesis of Type XI collagen. Whereas, alteration in COL11A2 allele causes systemic Stickler phenotype without ophthalmic manifestations.[14]

Alport syndrome

Leonhard G. Guthrie (1902) introduced a family in which a handful of members had hematuria. He observed that hematuria had been inherited from the mother side only. The disease was then titled “Idiopathic,” or “congenital, hereditary, and family hematuria.” The members of the same family had follow-up after 10 years in 1912 by researchers George Kendal and Arthur F. Hertz and later in 1923 were followed up by Arthur F. Hurst. They entitled the disease “Hereditary familial congenital haemorrhagic nephritis.”[15] Alport syndrome outlined by Alport in 1927 is distinguished by features such as hematuria and hearing impairment in young men with a kidney failure history in family. Patients with progressing kidney failure show microscopically histopathological features of highly layered glomerular basal lamina, with replicated lamina densa. The inadequacy is due to one or more alterations in genes related to Type IV collagen, pointing toward physical composition and regulatory modifications regarding basal lamina in the kidney, lens, or cochlea. The six alike forms of Type IV collagen protein are coded by six genes on distinct chromosomes: collagen Type IV alpha-1 chain and alpha-2 chain encoded on chromosome 13, collagen Type IV alpha-3 chain and alpha-4 chain related to chromosome 2, whereas collagen Type IV alpha-5 chain and alpha-6 chain encoded on X chromosome.[16] The α-chains peculiarly α3, α4, and α5 may be missing due to the alterations in one of the subunits of Type IV collagen protein-related genes. Alport syndrome is genetically discovered by the defect located on chromosome COL4A5 gene. Subsequently, deposition of Type V and VI collagen in the basal lamina of the glomerulus is seen in reaction. In future, malformation in the absorption and pathological thickening of the kidney tissue will cause its failure.[17]

Marfan syndrome

A French doctor, Antonine Marfan Antoine Bernard-Jean Marfan, reported a syndrome in a 5½-year-old girl in 1896.[18] It is liable to change autosomal dominant disorganization of tissues of mesodermal origin in which principal features have an effect on circulatory system, ocular system, and skeleton.[19] Many practitioners have a basic information regarding Marfan syndrome, a comparatively common congenital disorder of mesenchymal tissue with clinical symptoms involving the contractile system, vessels, metabolism, and ocular and cutaneous systems.[20] The pathological mechanisms are not totally explained. Nevertheless, fibrillin-1 factor alterations area unit presumed to show a contradictory result.[21] The abnormal equilibrium is believed to end in tube-shaped structure transforming characterized by associate degree-inflated elastosis as results of more estimated Type 2 and Type 9 matrix metalloproteinases and multiplied hyaluronan components which steadily degenerate scleroprotein fibers and different parts of the extracellular matrix. In Marfan syndrome, a crucial part is played by transforming growth factor-beta (TGF-β). Extracellular matrix glycoprotein fibrillin-1 attaches to an inactive type of TGF-β and isolates itself from performing its functions.[22]

Epidermolysis bullosa

Epidermolysis bullosa is a cluster of uncommon hereditary disorders portrayed by the presence of perennial blistering ensuing from even minor traction of epithelial-lined surfaces, most remarkably the skin.[23] Over one half junctional epidermolysis bullosa cases are caused by one among two perennial nonsense mutation within the LAMB3 sequence that is useful for alteration analysis and antenatal testing. Dystrophic epidermolysis bullosa so far has been related altogether cases with alterations of the sequence cryptography to sort Type VII collagen.[24] Skin disorders of the epidermolysis bullosa cluster, described by skin delicacy, precisely instigated wrinkles and disintegrations of the skin and mucous surfaces. COL7A1 is the solely optimum, actuating sequence, and flexibility is provided by the very fact that collagen VII is integrated by both keratinocytes and fibroblasts.[25]

Systemic sclerosis

Systemic sclerosis is an extraskeletal tissue ailment of the immune system starting point, portrayed by vascular changes and dynamic skin and instinctive fibrosis influencing essentially organs such as lungs, digestive tract, kidneys, and heart.[26] Systemic sclerosis is connected to interferon regulatory factor 5, signal transducer and activator of transcription 4 (STAT4), protein tyrosine phosphatase, nonreceptor Type 22 and B-cell scaffold protein with ankyrin repeats 1, connective tissue growth factor, T-box transcription factor, Corf13-BLK, interleukin-10 receptor (IL-10R), IL-23R, and tumor necrosis factor superfamily (TNFSF4).[27]

Oral submucous fibrosis

Oral submucous fibrosis (OSMF) is a constant, enervating ailment presented by juxta-epithelial thickening of the oral cavity, recently classified under one of the potentially malignant conditions. It is a condition which has an effect on any part of the oral cavity and may extend into the pharynx. OSMF leads to the development of vesicles and is always in association with a juxta-epithelial inflammatory response accompanied by a change in fibrous and elastic components of lamina propria along with atrophic epithelium that proceeds to inelasticity of the oral mucosa and induces trismus and difficulty while eating.[28] Four alkaloids are decisively noted in the investigations performed biochemically such as arecoline, arecaidine, guvacine, and guvacoline; among these, the chief component is arecoline. The alkaloid compound of the areca nut invigorates the inflammatory process. An underlying epithelial inflammation is accompanied by fibro-elastic changes in the lamina propria. Epithelial atrophy and increase in collagen produce thick dense fibrotic bands. The factors involved in the pathogenesis of OSMF are role of areca nut alkaloids, presence of copper leading to multiplication of fibroblasts and escalating collagen production, modifying collagen configuration by tannins and fibrogenic cytokines, a discontinuous genetic variation leading to OSMF, and function of collagen-related factors, i.e., COL1A2, COL3A1, CoL6A1, COL6A3, and COL7A1.[29]


It is a clinical syndrome caused by the deficiency of ascorbic acid or Vitamin C. Ascorbic acid is not formed in the human body, so it is obtained through diet. Several tissues such as skin, bone, and cartilage require Vitamin C for their purposeful functioning. Major sources are citrus fruits and leafy vegetables. Daily intake is 30–200 mg/day. Deficit amount of Vitamin C causes hindrance in collagen biosynthesis. Ascorbic acid supports in many mechanisms acting as an enhancer. One of them is procollagen synthesis by hydroxylation of L-pro and L-lys residues. During the process, Vitamin C acts as a catalyst. Deficiency of ascorbic acid during this process leads to the formation of abnormal collagen which presents the features of scurvy in the form of compromised healing of wounds, lack in the activity of osteoblasts and fibroblasts, edema, weakening of periodontal ligament, loosening of teeth, impaired dentin formation, hemorrhage, and exhaustion.[30],[31]

Lupus erythematosus

Bullous type of LE is associated with vascular or collagen connective tissue disorder. Immunohistochemically researchers may have proved the presence of antibodies for Type VII collagen along with immunoglobulin deposits. The chief epitope responsible is fibronectin Type III homology region of NC1 domain of Type VII collagen. It acts as a mediator among anchoring fibrils at dermal epidermal junction and the various ground substance proteins. During the interaction, antibody involvement leads to instable anchoring fibrils of Type VII collagen and forms a blister. Other features are fever, weight loss, macular rash in shape of butterfly, and oral symptoms such as ulceration, pain, erythema, and hyperkeratosis.[32],[33]

  Conclusion Top

Collagen is known as the foundation element of the body, existing in different skeletal and extraskeletal tissues. The crucial functions of collagen are related to the diseases that are originating by the gene alterations encoding them. In later years, in spite of all gathered improved knowledge regarding the architecture and formation of collagen, the inherited and molecular levels of the collagen disorders, which are recognized as irrecoverable clinical syndromes, continue to exist unresolved. Furthermore, the capability to understand various molecular level diseases, the advanced biochemical investigations, molecular findings, and the HiTech assets will ease in clarification of the structured and pathophysiological activities.

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Conflicts of interest

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