Connective tissue


Connective tissue is the most abundant type of tissue in the body. It serves to connect and support other tissues and also has regulatory and immunologic functions. Connective tissue consists of cells, mainly fibroblasts, and an extracellular matrix (ECM). The specific composition of the ECM determines the biochemical properties of the connective tissue. There are many different types of connective tissue, with loose and dense connective tissue being the most common.

Disorders of connective tissue are discussed in detail in the connective tissue diseases article.


Connective tissue consists of specialized cells that are embedded in the extracellular matrix (ECM). Connective tissue is classified as loose or dense connective tissue depending on the ratio and structure of its components.

Cells of the connective tissue

Resident cells

Transient immune cells

Extracellular matrix

The extracellular matrix (ECM) is composed of various macromolecules arranged in a three-dimensional structure. Its specific composition determines the biochemical properties of the connective tissue.

Extracellular matrix fibers (connective tissue fibers)

Collagen molecules are the basis of collagen fibers and reticular fibers. They account for the majority of proteins in the ECM, which makes them the most abundant proteins in the human body. Elastic fibers are composed of elastin molecules and can be found together with collagen fibers in tissues that require elasticity in addition to tensile strength, e.g., the lung.

Collagen fibers Reticular fibers Elastic fibers
Main molecule
  • Tensile strength
  • Tensile strength with limited elasticity
  • Elasticity
Associated proteins

Marfan syndrome is caused by a mutation in the fibrillin gene (FBN1)!


Collagen types

Collagen types Tissue distribution Related conditions
Type 1 collagen
Type 2 collagen
  • Achondrogenesis (type II)
Type 3 collagen
Type 4 collagen
Type 5 collagen

Type ONE collagen is in bONE. Type TWO collagen: carTWOlage. Type THREE collagen is deficient in the vascular type of Ehlers-Danlos syndrome (ThreE D). Type FOUR collagen is under the FLOOR (part of basement membrane).

Collagen synthesis

Stages Process Site Intermediate product (precursors of collagen)
1. Translation
  • Synthesis of polypeptide chain (pro-α chain with repeating Gly-X-Y sequence) and further processing
IC (rER) Preprocollagen
2. Hydroxylation IC (rER) Procollagen (pro-α chain)
3. Glycosylation IC (rER)
4. Formation of a triple helix
  • Formation of disulfide bonds and hydrogen bonds between three α-chains to form a triple helix
  • Function: requirement for fibril formation (fibrillogenesis)
IC (rER) Procollagen (triple helix)
5. Exocytosis
  • Exocytosis of the collagen triple helix into the extracellular space
6. Proteolytic processing
  • Cleavage of the procollagen at the C-terminus and N-terminus
  • Function: Collagen molecules become insoluble in water.
EC Tropocollagen
7. Fibrillogenesis (cross-linking) EC Collagen fibrils
8. Formation of fibers EC Collagen fiber (end product)
Abbreviations: IC = intracellular; EC = extracellular; ECM = extracellular matrix; rER = rough endoplasmic reticulum

Vitamin C deficiency leads to scurvy because it impairs hydroxylation of procollagen chains.

Impaired triple helix formation during collagen synthesis is the pathophysiological mechanism of osteogenesis imperfecta.

Ehlers-Danlos syndrome is caused by defective cleavage of procollagen molecules.

Menkes disease occurs as a result of defective cross-linking of tropocollagen.


Defective α1-antitrypsin leads to increased elastase activity, which results in the autosomal codominant disorder α1-antitrypsin deficiency.

Normal aging entails decreasing levels of dermal collagen and elastin along with a decreased synthesis of collagen fibrils.

Glycosaminoglycans (GAGs)


Glycoproteins of the ECM

Proteoglycans are primarily composed of carbohydrates that are attached to the side of a small core protein! In contrast, glycoproteins are mainly composed of a protein that is attached to the side chain of a short carbohydrate!


Connective tissue types

Type Main components Function Occurrence
Loose connective tissue
  • Structural framework for organs (interstitium)
  • Attaches epithelia to underlying tissue
  • Allows for independent movement
Dense connective tissue
  • Provide tensile strength, especially in tissue under mechanical stress
Reticular connective tissue
Elastic ligaments
  • Provides ligaments with a high level of elasticity
Mucous connective tissue
Stroma of ovary

Clinical significance

  • 1. McKusick VA, Kniffin CL. Achondrogenesis, type II; ACG2. url: Accessed July 16, 2018.
  • 2. Sobreira N, McKusick VA. Ehlers-Danlos Syndrome. Updated May 30, 2018. Accessed July 16, 2018.
  • Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. New York: Garland Science; 2014.
  • Karsdal M. Biochemistry of Collagens, Laminins and Elastin. Academic Press; 2016.
last updated 11/19/2020
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