Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force resistance to the tissue.

Apart from providing mechanical support and hydration to cells, an important role of the ECM is to communicate with cells. Molecules in the ECM communicate with cell adhesion molecules like integrins which, when activated, cause a signaling cascade that can result in alterations of cytoskeletal proteins in cells. Therefore, signaling from the ECM can ultimately alter cell proliferation, differentiation, migration, polarity, and gene expression. ECM is also a reservoir for bioactive molecules like cytokines and growth factors. Various signals can cause the ECM to sequester these bioactive molecules and form concentration gradients thereby regulating their bioavailability.

ECM is secreted by the primary cells of the connective tissue. For example, chondrocytes in cartilage secrete ECM rich in chondroitin sulfate and hyaluronic acid while osteoblasts in bone secrete ECM rich in collagen. In healthy tissue, ECM is constantly remodeled by the regulated breakdown of its components by enzymes such as matrix metalloproteases (MMPs) and MMP inhibitors secreted by fibroblasts. This dynamism of ECM ensures its strength, compression resistance, and elasticity. However, in aged tissues, fibroblasts become old and resistant to apoptosis and secrete more MMPs and cytokines, giving rise to inflammation. This alters the integrity of the fibers resulting in stiffening and loss of elasticity of the matrix during aging. Due to its abundance and pervasiveness across the body, ECM plays a causative role in several connective tissue disorders, muscular dystrophy, fibrosis, and cancer.

This text is adapted from Openstax, Anatomy and Physiology 2e, Section 4.3:Connective Tissue Supports and Protects