type II collagen

STRUCTURE AND SYNTHESIS: Type II collagen is a fibrillar collagen. It is a homotrimer of three α1(II) chains, which form a triple helix with a Gly-X-Y repeat. Glycine is needed every third residue for tight helix packing. The gene is COL2A1 on chromosome 12. Steps of synthesis (shared with other fibrillar collagens): (1) Preprocollagen is made on the rough ER. (2) Hydroxylation of proline and lysine in the ER requires vitamin C (ascorbate) as a cofactor. (3) Glycosylation of hydroxylysine and triple-helix formation produce procollagen, which is secreted. (4) Extracellular procollagen peptidases cleave the terminal propeptides to give tropocollagen. (5) Lysyl oxidase (requires copper) cross-links tropocollagen into fibrils. Chondrocytes synthesize it.

LOCATION: Type II collagen is found in hyaline cartilage (articular cartilage, trachea, costal cartilage, growth plate), the nucleus pulposus of the intervertebral disc, and the vitreous humor of the eye. It is also found in the inner ear. Fibrocartilage (annulus fibrosus, menisci) is mostly type I collagen. The mnemonic "type tWo = carTWOlage" works for cartilage.

COLLAGEN TYPES (high-yield comparison): - Type I: bone, skin, tendon, dentin, fascia, cornea, late wound repair. Defective in osteogenesis imperfecta. - Type II: cartilage, vitreous, nucleus pulposus. - Type III (reticulin): skin, blood vessels, uterus, fetal tissue, granulation tissue and early wound repair. Defective in vascular Ehlers-Danlos syndrome. - Type IV: basement membrane and basal lamina. Defective in Alport syndrome and targeted in Goodpasture syndrome.

CLINICAL CORRELATIONS: - Achondrogenesis type II and hypochondrogenesis, spondyloepiphyseal dysplasia congenita, and Kniest dysplasia are caused by COL2A1 mutations. They produce skeletal dysplasia with short-trunk dwarfism. - Stickler syndrome (often COL2A1, autosomal dominant) causes ocular findings (high myopia, vitreoretinopathy, retinal detachment, cataracts), a flat midface, cleft palate or Pierre Robin sequence, sensorineural hearing loss, and early-onset arthropathy. Types XI and IX collagen mutations can also cause it. - Osteoarthritis: type II collagen is degraded by matrix metalloproteinases (collagenases), and cartilage loss occurs with aging, mechanical stress, and inflammatory cytokines (IL-1, TNF-α). - Relapsing polychondritis: autoimmune inflammation of cartilage (ears with sparing of the lobule, nose, and tracheobronchial tree) with antibodies to type II collagen. It presents with a painful, red, swollen ear and can cause saddle-nose deformity and airway collapse. - Rheumatoid arthritis: anti-type II collagen antibodies are found, and type II collagen-induced arthritis is a classic animal model. - Type II collagen is a target in the vitreous. Vitreous liquefaction with aging can lead to posterior vitreous detachment (floaters and flashes).

KEY TAKEAWAYS FOR BOARDS: Cartilage = type II. Defects cause chondrodysplasia and Stickler syndrome. Anti-type II collagen antibodies are seen in relapsing polychondritis. Vitamin C deficiency (scurvy) impairs hydroxylation of all fibrillar collagens, and copper deficiency or Menkes disease impairs cross-linking via lysyl oxidase.