Collagen and Connective-Tissue Disorders
Collagen Structure and Synthesis
Collagen is a major structural protein of connective tissue, bone, skin, tendons, ligaments and the periodontal supporting tissues.
Collagen synthesis
- Pro-α chains are synthesized in the rough endoplasmic reticulum.
- Proline and lysine residues undergo hydroxylation.
- Selected hydroxylysine residues are glycosylated.
- Three chains form a triple helix called procollagen.
- Procollagen is secreted extracellularly.
- Terminal propeptides are removed to form tropocollagen.
- Tropocollagen molecules assemble into fibrils.
- Lysyl oxidase forms cross-links that strengthen collagen fibers.
Cofactors and enzymes
| Step | Enzyme/cofactor | Importance |
|---|
| Hydroxylation of proline and lysine | Vitamin C, Fe²⁺ and oxygen-dependent enzymes | Stabilizes collagen triple helix |
| Glycosylation | Glycosyltransferases | Modifies selected hydroxylysine residues |
| Procollagen processing | Extracellular procollagen peptidases | Produces collagen molecules capable of fibril assembly |
| Cross-linking | Lysyl oxidase, copper-dependent | Strengthens fibrils |
Major collagen types
| Type | Main locations | Key association |
|---|
| I | Bone, skin, tendon, dentin | Most abundant collagen |
| II | Hyaline cartilage and vitreous body | Cartilage |
| III | Reticular fibers, blood vessels and some hollow organs | Reticular framework |
| IV | Basement membranes | Sheet-like network |
| V | Placenta, cornea and tissues containing Type I collagen | Fibril assembly regulation |
Collagen Disorders
| Disorder | Main mechanism | Classic clue |
|---|
| Osteogenesis imperfecta | Usually Type I collagen abnormality | Fragile bones, fractures and sometimes blue sclerae |
| Ehlers–Danlos syndromes | Heterogeneous defects in collagen synthesis, processing or related proteins | Hypermobile joints and hyperextensible skin |
| Scurvy | Vitamin C deficiency impairs collagen hydroxylation | Bleeding gums, petechiae and poor healing |
| Menkes disease | Defective copper transport reduces copper-dependent enzyme activity | Hair abnormalities and connective-tissue defects |
| Alport syndrome | Type IV collagen gene abnormalities | Hereditary nephritis, hearing loss and ocular abnormalities |
Dental relevance
- Vitamin C deficiency can impair gingival integrity, periodontal tissue maintenance and wound healing.
- Osteogenesis imperfecta may affect dentin, producing dentinogenesis imperfecta in some patients.
- Ehlers–Danlos syndromes may involve fragile tissues and periodontal abnormalities in selected subtypes.
Remember: Vitamin C supports hydroxylation; copper supports lysyl oxidase-mediated cross-linking.
