In normal healthy tissues where the collagen is fully hydroxylated and in a triple helical structure, the molecule is resistant to attack by most proteases. Under these normal healthy conditions, only specialized enzymes called collagenases can attack the collagen molecule.
The group of collagenases belong to a family of enzymes called matrix metalloproteinases or MMPs.
Many cells in our body can synthesize and release collagenase including fibroblasts, macrophages, neutrophils, osteoclasts, and tumor cells. One of the reasons that some cancer cells can be so invasive is because they release potent collagenases that can break down the collagen around them.They can also break down the basement membranes of blood vessels and spread throughout the body. In chronic pressure ulcers, there is a massive invasion of neutrophils, and they release a very potent collagenase called MMP-8 that is responsible for connective tissue breakdown.
Physiological turn over
During growth and development, the collagen fibrils in all tissues undergo repeated synthesis, degradation, and resynthesis. In adults, collagen fibers in most tissues undergo very little metabolic turnover. One exception is bone where collagen fibrils are degraded and resynthesized as part of lifelong remodeling.
Increased collagen degradation occurs with advancing age and also in sun exposed areas. Loss of elasticity and strength results in sagging skin and wrinkles. However, collagen maintains its structural integrity for longer if it is protected from environmental threats like UV exposure.
Variations in collagen turn over
A) The rate of collagen degradation increases under some circumstances
I) In starvation, a large fraction of the collagen in skin and other connective tissues is degraded, thus providing amino acids for gluconeogenesis .
2) Large losses of collagen also occur in most connective tissues during immobilization or prolonged periods of low-gravitational stress.
3) In rheumatoid arthritis, a rapid degradation of collagen occurs in the articular cartilage.
4) In cancer and chronic nonhealing ulcers, the extent of collagen degradation can be quite extensive
B) Deceased collagen synthesis
Glucocorticoids decrease the collagen content of most connective tissues, including bone, by decreasing the rate of collagen synthesis. Decreases in collagen weaken tissues.
C) Excess collagen deposition
In many pathologic states, however, collagen is deposited in excess.
1) Post inflammation- With injury to tissue, inflammation is usually followed by increased deposition of collagen fibrils in the form of fibrotic tissue and scars.
2) Post repair- The deposition of collagen fibrils during the repair process is largely irreversible and is a major feature of the pathological changes in hepatic cirrhosis, pulmonary fibrosis, atherosclerosis, and nephrosclerosis.
Disorders associated with collagen synthesis
A number of genetic diseases result from abnormalities in the synthesis of collagen. Some diseases are due to mutations in collagen genes or in genes encoding some of the enzymes involved in these posttranslational modifications (Table).
Table – Diseases caused by mutations in collagen genes or by deficiencies in the activities of enzymes involved in the posttranslational modification of collagen
|Gene or Enzyme||Disease|
|COL1A1, COL1A2||Osteogenesis imperfecta, type 1|
|Ehlers-Danlos syndrome type VII autosomal dominant|
|COL3A1||Ehlers-Danlos syndrome type IV|
|COL7A1||Epidermolysis bullosa, dystrophic|
|COL10A1||Schmid metaphysial chondrodysplasia|
|Lysyl hydroxylase||Ehlers-Danlos syndrome type VI|
|Procollagen N-proteinase||Ehlers-Danlos syndrome type VII autosomal recessive|
|Lysyl hydroxylase(Secondary to deficiency of copper)||Menke’s disease|
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