Connective Tissue: Cells, Fibers and Extracellular Matrix

Connective Tissue Disorders: Introduction

Connective tissue (CT) is the first and most abundant type of tissue in the body, composed of macromolecules that form the "matrix" surrounding cells. It is found throughout the body and forms specialized structures such as cartilage, tendons, and bones, among others.

In addition to its support function, connective tissue regulates the behavior of the cells it contains, influencing their differentiation, development, migration, and shape. Connective tissue cells produce the extracellular matrix, which is composed of fibers and ground substance.

Connective Tissue Support Cells

The cells of connective tissue are immersed in an extracellular matrix, the composition of which determines their characteristics. Their presence or absence depends on the type of tissue.

Matrix-Producing Cells

Connective tissue cells are mainly derived from the mesoderm, though some come from the ectoderm. They share structural features, such as adhesion mechanisms that interact with the matrix and with other cells. These cell populations represent the fixed cells of connective tissue, where connective tissue cells constitute the predominant component.

1. Mesenchymal Cells

Morphologically, mesenchymal cells are star-shaped with long, thin processes that make contact with neighboring cells through gap junctions. They are located in the embryonic mesenchyme, and in the adult they persist as multipotent mesenchymal cells, which are usually located near blood vessels, where they receive the name of adventitial cells. Functionally, they are the stem cells of connective tissue. Their mitotic index is high and they have the property of multipotentiality with respect to differentiation.

2. Fibroblasts

Concept and location: Fibroblasts are specific cells of common connective tissue and are responsible for the synthesis of extracellular matrix. When connective tissue develops or repairs, fibroblasts are produced from mesenchymal cells.

Structure: In culture they display a stellate morphology, and in tissue they are fusiform. Their nucleus is large and central, and the cytoplasm is basophilic.

Function: They synthesize the matrix, resist aggression, are actively capable of dividing, and participate in the tissue repair reaction. They can transform into histiocytes, adipocytes, smooth muscle cells, and others.

Types: Myofibroblasts share typical features with fibroblasts and smooth muscle cells. They are located in the capsule of the suprarenal gland, testicles, seminiferous tubules, and others.

Pericytes: They are located in the walls of capillaries and some venules and arterioles. They participate in the formation of the capillary basal lamina and the venule wall.

3. Chondroblasts/Chondrocytes

Concept and location: In the tissue of cartilage, where they work as specific cells that synthesize the matrix when they are fully differentiated, they are called chondrocytes. Their origin is mesodermal.

Structure: They are similar to epithelial cells, surrounded by intercellular substance.

4. Chondroblasts/Chondrocytes

Concept and location: In the tissue of cartilage, where they work as specific cells, solid and not mineralized, when they are fully differentiated they synthesize the matrix and are called chondrocytes.

Structure: Chondroblasts have an oval, rounded morphology and show a central nucleus with loose chromatin. Chondrocytes present a variable appearance; they remain in lacunae carved in the same matrix. All cells originate from a single mitotic division of chondroblasts, and their arrangement depends on the plane of division.

5. Osteoblasts/Osteocytes

Concept and location: These are the cells that secrete the tissue that forms bone. They take care of the bone matrix, which rapidly transforms into bone through the deposit of calcium phosphate salts.

Structure: Osteoblasts have an epithelial appearance and signs of very active metabolism, forming a layer on the bone surface. Osteocytes are cells equipped with long, narrow processes, with an oval nucleus, organelles, and poor cytoplasm. They contain lysosomal enzymes and participate in osteolytic activity, regulating phospho-calcium balance.

6. Cells that Produce Dental Tissues

• Ameloblasts: enamel
• Odontoblasts: dentin
• Cementoblasts: cementum

All of these derive from the mesoderm, except ameloblasts, which are of ectodermal origin.

Macromolecules of the Extracellular Matrix

a.) Fibrous proteins:

1. Collagen: (General concepts): Its composition is about one-third glycine, with proline and hydroxyproline also prominent. Collagen molecules, biochemically, are subunits formed by tropocollagen: a helical structure with three polypeptide chains intertwined.

(Types):

• Type I: 2 α1 chains and 1 α2 chain. Mostly located in deep tendons and bones, forming large sets of resistant fibers.
• Type II: 3 α1 chains. Found in cartilage. Forms only fine fibers.
• Type III: 3 α1 chains. Forms reticular fibers in skin.
• Type IV: 3 α1 chains. Forms sheets found in basal laminae.
• Type V: 2 α1 chains, 1 α2 chain and 1 α3 chain. Found in small amounts and distributed diffusely in tissues, forming thin fibers.
• Type VI: 3 α chains. Forms thin fibrils.
• Type VII: short fibrils that form anchoring plates in the basal skin.

(Synthesis): Collagen synthesis begins in the cells that produce it, and the polymerization of subunits constitutes fibrils, which aggregate to form fibers in the extracellular space. As tropocollagen subunits polymerize, collagen fibrils originate, which aggregate into thicker fibers. The formation of collagen depends on hydroxylation of amino acids in the extremes of the molecule.

(Collagen fibers): They appear as whitish bundles forming undulating courses. They are very resistant to traction, flexible, and slightly elastic. They are found in connective tissue of support of organs that bear large traction forces. When observed under the microscope, they are dispersed, arranged in bundles. Electron microscopy shows that fibers result from the aggregation of microfibrils with transverse striations.

(Reticular fibers): Collagen fibers covered by a protein and glycolipid layer. They form fine fibers that prevent aggregation into larger calibers. They tend to form networks. They are located in lymphoid tissue, bone marrow, and organs.

2. Fibrillin: A glycoprotein forming fibrils that constitute the main component of extracellular microfibrils. It is associated with elastin, forming elastic fibers. It is found mainly in the glomeruli of the kidney and the spleen.