Connective tissues are composed of cells and their surrounding extracellular matrix. They are derived from the mesenchymal component of the embryonic mesoderm. In spite of this common origin, there are some noticeably different structural types (e.g., blood and bone). Each type, however, is made up of the same components, namely tissue-forming cells, which are not usually in contact with one another, and an extracellular matrix (ECM). The ECM provides a physical scaffold around the connective tissue cells which may attach to the matrix for support. The nonfibrous components of the ECM include glycosaminoglycans (GAGs) and glycoproteins (GPs). The fibers of the ECM include collagen, elastic, and reticulin fibers. All matrix molecules also play some additional bioactive role in the differentiation of precursor connective tissue cells and the regulation of their activity. Some of these bioactive components have been called matricellular proteins, describing their dual function.
The extracellular spaces of all vertebrates are taken up by water and very large molecules called glycosaminoglycans, previously referred to as mucopolysaccharides. As the name suggest, these molecules are polymers of a variety of polysaccharides (Greek glykis = sweet). The polymer unit is a disaccharide made up of a glucosamine (amino sugar) and either a glycan (uronic sugar) or galactose. Some GAGs are covalently linked to a protein core in an arrangement like a bottle brush (▶ Fig. 6.1).
Hyaluronic acid: This molecule has been called the “goo” that holds tissue together. It has important properties which make it particularly suitable as a lubricant in synovial fluid. It is viscoelastic, which means that it may respond to loads with both elastic rebound and viscous resistance. When a joint is suddenly loaded, it induces an elastic response from the synovial fluid, which protects the joint from damage. Loads which are less rapidly applied allow the synovial fluid to flow and the joint to move freely. Hyaluronic acid also surrounds and protects cartilage cells from compression.
This GAG is one of the few which is nonsulfated and not linked to a protein core. Hyaluronic acid may be a huge molecule of molecular weight 100,000 to 10 million. It is in the form of a long loosely tangled chain (▶ Fig. 6.1). It occurs in most connective tissue but is a vital component of synovial fluid.
Chondroitin sulfate: This GAG is found in bone, cartilage, the periodontal ligament and the dental pulp. It is a smaller molecule than hyaluronic acid, though as with other GAGs, the molecular weight varies depending on the source and the stresses being applied to it.
Water retention: The most important property of GAGs is to bind or trap relatively large amounts of water, about 60% of the total content of water in soft tissue structures. This maintains the turgidity of skin and other structures. Water retention also accounts for the ability of GAGs to resist compression as the water molecules are unable to be squeezed out of the entangled meshwork that characterizes GAGs.
Resist compression: While the fibrous component of connective tissue resists tensile forces, GAGs resist compressive forces. This together with their slipperiness makes them an important component of synovial fluid and contributes along with collagen to the load-bearing capacities of cartilage.
Concentrated ions: GAGs have the ability to concentrate calcium ions, many times more than the surrounding tissue, because of the large number of charged particles within the meshwork of the molecule. The role of GAGs in the pulp may be to assist calcification of secondary dentin and to protect the pulp from vibration. Inflammatory exudate in the pulp may be absorbed by GAGs and so prevent build-up of pressure.
GPs are polymers consisting of long chains of covalently linked polypeptides (amino acid residues). Short carbohydrate (CHO) side chains of about 7 to 10 sugars are linked to the peptide. The side strings of sugar usually end with sialic acid, giving the carbohydrate side chain a negative charge (▶ Fig. 6.2). Neighboring ends of sialic acid repel each other, and this tends to keep the whole molecule straightened out and away from adjacent GP molecules. The large molecules are therefore long and slippery like buttered spaghetti. The amount of CHO side chain varies. It may be as little as 5% and as much as 50% in salivary GPs. This high CHO content in salivary GPs is important in providing the ionic bonds with enamel which form pellicle. GPs in saliva provide good lubrication and a source of sugars, which bacteria can utilize. GPs have a wide range of other functions apart from their importance in saliva.
They are the markers on the cell membranes of red blood cells. These markers confer the four major types of blood, A, B, AB, and O. They also form part of the cell wall of bacteria to which antibiotics can attach. While GPs do not form a large component of the extracellular matrix like GAGs do, they are of great importance as they interact with cells to regulate their differentiation and activity.
Bone sialoprotein (BSP) has, as the name suggest, a large proportion of sialic acid. It appears in osteoid of embryonic (woven) bone and may be important with the other noncollagen bone proteins in initiating mineralization.
Osteonectin is a strongly acidic glycoprotein, which is readily phosphated and binds strongly to hydroxyapatite. Synthetically produced osteonectin increases the rate of bone regenerating properties when applied to healing bone.