Tendon & Ligament  - Development and Stem Cells

Embryonic Development of the Tendon and Ligament:

The tendon is a fibrous contractile tissue which connects muscle to bone, enables joint movement and maintains articular stability by transmitting the force created by muscle contraction to the bone. 

During the course of embryonic development, mesenchymal progenitor cells originating from the somites, undergo differentiation to form primary tendon structures. In the mouse, tendons are established at E14.5, when fibrillogenesis begins, and fibrillar extracellular matrix is first recognizable at E18. From E14.5 to P4, the tendon is comprised of a homogenous population of short, small-diameter protofibrils. Mature fibrils grow from protofibrils and assemble via end-to-end and lateral fusion.

Anatomical Structure and Function of the Tendon and Ligament:

Mature tendons are shiny white and have a fibro-elastic texture. They are resistant to tension and compression forces. Ligaments connect bones and are structurally similar to tendons. The difference between tendon and ligament is mainly functional; no embryonic origin distinct from that of tendon has been described for ligaments. 

Tendons and ligaments consist of collagen fibers, and elastin, embedded in a proteoglycan-water matrix. Collagen I comprises 65-80% and elastin 1-2% of the dry tendon mass. The low proportion of elastin enables transmission of the tension force to the bone and prevents excessive stretching of the tendon. The non-fibrillar components of tendon are proteoglycans (PGs) and glycoproteins (GPTs). Decorin and fibromodulin are the most important PGs in the tendon/ligament, and are thought to regulate the diameter of the collagen fibrils. Fibronectin, thrombospondin, tenascin-C and undulin are the most prevalent GPTs in tendons.

The collagen fiber is the basic unit of tendon and is comprised of a number of collagen fibrils. Tenocytes, cells responsible for the production of all tendon extracellular matrix components, lie between the collagen fibers.  A cluster of collagen fibers forms a primary fiber bundle called the subfascicle, which in turn cluster to form the fascicle, which is a secondary fiber bundle. Fascicles comprise tertiary fiber bundles. Each collagen fiber and primary, secondary and tertiary bundle is enveloped by thin connective tissue called endotenon. The endotenon network allows groups of fibers to slide on each other. It also carries nerves, blood and lymphatic vessels to the inner portion of the tendon. Finally, groups of tertiary fiber bundles form the tendon unit enclosed in epitenon – a sheath of fine connective tissue composed of collagen strands.

At the level of fascicle, the crimp of the fibril, defined as its waviness, which is achieved by altered fiber patterning, is a structural characteristic that plays a significant role in the mechanics of the tendon. The crimp enables adaptation of tendon to nonlinear mechanical stress.

Each muscle features a proximal and distal tendon. Tendons are connected to muscles at the myotendinous junction (MTJ). The main components of the MTJ extracellular matrix are laminin, integrin, vinculin, fibronectin and talin, which support strong connections between the muscle actin filaments and the tendon collagen fibers.

The enthesis or osteotendinous junction (OTJ) is the area where tendons connect to bones, and is essential for proper functioning of the musculoskeletal system, as it transmits muscle-generated force to the bone skeleton. 

Embryonic Development of the Tendon and Ligament:

The tendon is a fibrous contractile tissue which connects muscle to bone, enables joint movement and maintains articular stability by transmitting the force created by muscle contraction to the bone. 

During the course of embryonic development, mesenchymal progenitor cells originating from the somites, undergo differentiation to form primary tendon structures. In the mouse, tendons are established at E14.5, when fibrillogenesis begins, and fibrillar extracellular matrix is first recognizable at E18. From E14.5 to P4, the tendon is comprised of a homogenous population of short, small-diameter protofibrils. Mature fibrils grow from protofibrils and assemble via end-to-end and lateral fusion.

Physiology of the Tendon and Ligamnet:

Tendon injuries are common clinical problems, with rupture of the Achilles tendon being the most frequent type of tendon trauma. In addition to sport activities as the cause of injury, excessive or absence of application of tension on the tendon can lead to alteration of its properties and to formation of lesions. Impaired tendon function is also a function of age, diabetes, hormone imbalance and others. In general, the density and total mass of collagen increases and the water and PG content decrease with age, leading to tendon "stiffness". To date, no effective treatment exists for restoration of injured tendons.