Connective tissue

Last updated: August 15, 2022

Summarytoggle arrow icon

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 “Connective tissue diseases

Overviewtoggle arrow icon

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 tissuetoggle arrow icon

Resident cells

Transient immune cells

Extracellular matrixtoggle arrow icon

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.

Overview of extracellular matrix fibers
Collagen fibers Reticular fibers Elastic fibers
Main molecule
  • Tensile strength
  • Tensile strength with limited elasticity
  • Elasticity
Associated proteins
  • Fibrillin
  • Fibulin-5

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


Types of collagen
Tissue distribution Related conditions
Type I collagen (90% of body collagen)
Type II collagen
  • Achondrogenesis (type II) [2]
Type III collagen (reticulin)
Type IV collagen
Type V collagen
  • Degradation: enzymatic via specific collagenases (zinc-dependent proteinases that belong to the matrix metalloproteinases family)
  • Synthesis: Collagens are synthesized at the rough ER (rER) and undergo extensive post-translational modifications.
Overview of collagen synthesis
Stages Process Site Intermediate product (precursors of collagen)
1. Translation
  • Preprocollagen
2. Hydroxylation
3. Glycosylation
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)
  • Procollagen (triple helix)
5. Exocytosis
  • Exocytosis of the collagen triple helix into the extracellular space
  • IC → EC
6. Proteolytic processing
  • Cleavage of the procollagen at the disulfide-rich C terminus and N terminus regions
  • Function: Collagen molecules become insoluble in water.
  • EC
  • Tropocollagen
7. Fibrillogenesis (cross-linking)
  • EC
  • Collagen fibrils
8. Formation of fibers
  • EC
Abbreviations: IC = intracellular; EC = extracellular; ECM = extracellular matrix; rER = rough endoplasmic reticulum

Type ONE collagen is in bONE.
Type TWO collagen: carTWOlage
Type THREE collagen is deficient in the vascular type of Ehlers-Danlos syndrome (3D = ThreE D).
Type FOUR collagen is under the FLOOR (part of basement membrane).

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, resulting in the autosomal codominant disorder α1-antitrypsin deficiency, which is characterized by panacinar emphysema and cirrhosis.

Normal aging involves decreased levels of dermal collagen and elastin as well as decreased synthesis of collagen fibrils. Crosslinking is not affected by aging.

Glycosaminoglycans (GAGs)

  • Definition: a family of unbranched polysaccharide chains of repeating disaccharide units with multiple negative charges that constitute a large volume fraction of the ECM
  • Structure: polymer of repeating disaccharide units
    • First sugar: derivative of uronic acid (e.g., glucuronic acid)
    • Second sugar: hexosamine (e.g., the amino sugar N-acetylglucosamine)
  • Four main groups
    • Hyaluronic acid
    • Chondroitin sulfate and dermatan sulfate
    • Heparan sulfate
    • Keratan sulfate
  • Function
    • Bind H2O in connective tissue due to its negative charges: act as a cushion
    • Component of proteoglycans


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 typestoggle arrow icon

Types of connective tissue
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

Specialized connective tissue

  • Several tissue types in the body are primarily composed of connective tissue with a specialized ECM.
  • For further information on their special functions, please refer to the individual articles

Specialized connective tissuetoggle arrow icon

This section describes additional structures surrounding skeletal muscles that minimize friction during movement and maximize the transfer of force.



Synovial bursa


  • Definition: a thin layer of connective tissue that separates muscles and organs from other body structures
  • Function
    • Supports and protects muscles and internal organs
    • Reduces friction between muscles and is well-innervated to facilitate proprioception and nociception
  • Types

Muscle tissue


Bone tissue

Clinical significancetoggle arrow icon

Referencestoggle arrow icon

  1. Karsdal M. Biochemistry of Collagens, Laminins and Elastin. Academic Press ; 2016
  2. $Achondrogenesis, type II; ACG2.
  3. Ehlers-Danlos Syndrome. Updated: May 30, 2018. Accessed: July 16, 2018.
  4. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. Garland Science ; 2014

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