entheses (Figure 3.12c), some are primarily fibrous and noncartilaginous, although most tendon–bone attachments employ fibrocartilagenous entheses. The latter consist of four zones of connective tissue, listed in order from the tendon to the bone: (a) fibrous tissue originating from tendon (the aligned collagen fibrils surrounding fibroblasts resemble the tendon midbody), (b) uncalcified fibrocartilage, (c) calcified fibrocartilage, and (d) subchondral bone. This gradual change in structure reduces mechanical stress levels between the tensile tendon and the brittle bone.
Some tendons are also enclosed by tube‐like synovial sheaths, for example, at the wrist and ankle. These sheaths are made up of two layers, both lined by flattened synovial cells of mesenchymal origin. The inner visceral layer is attached to the surface of the tendon, while the outer parietal layer is adjacent to neighboring structures. The space between these layers contains a viscous fluid similar in composition to the synovial fluid of synovial joints. This liquid is composed of water, proteins, hyaluroanate, and other glycosaminoglycans. This synovial secretion acts as a lubricant permitting easy sliding movements of a tendon within its sheath. Tendinitis or tenosynovitis is an inflammation of this tendon sheath and are painful conditions that can follow trauma, excessive strain, or excessive exercise (see Chapters 2 and 11).
Tendons have a very rich neural network and are often innervated from the muscles with which they are associated or from local nerves. There are many nerve endings at the sites of myotendinous junctions and bone–tendon junctions, including Golgi tendon organs and free nerve endings (which are typically pain fibers), as discussed further in Chapter 4. With regard to vascularization, the interior of healthy tendons is fairly devoid of blood vessels, with most of the blood vessels localized to the tendon sheaths.
Function of Tendon Components
Transfer of forces
The myotendinous junctions and entheses described earlier facilitate force transfer between these structures. For example, the myotendinous junctions allow tendons to absorb sudden shocks in order to limit muscular damage (Selvanetti, Cipolla, & Puddu, 1997), and the entheses transfer muscle tensile forces across tendons and onto bone, enabling joint flexion. For this purpose, the collagen fibers of tendons are continuous with those in the endomysium and perimysium connective tissue layers in muscles, as well as with the periosteum of bones. However, tendons fibrils do not run continuously from muscle to bone. Instead, stress is transferred through a hydrated proteoglycan‐rich gel matrix in which the fibers of this fiber‐reinforced composite are contained (Ker, 2002; Shepherd & Screen, 2013).
Mechanotransduction in tenocytes
Tenocytes are stellate in shape when examined in longitudinal sections, with elongated protrusions in all directions. These protrusions contact tenocytes within the same and adjacent rows, thus forming an intricate tendon network. There are gap junctions at these contact points. Gap junction proteins, such as, connexin 43, are expressed at these sites and are thought to regulate the transfer of proteins between tenocytes via mechanisms that are still unclear. Yet, these gap junctions are considered essential mediators of the mechanotransduction function of tenocytes (mechanotransduction is defined as a cell’s response to mechanical cues by biochemical signals). Similar to other mechanosensitive cells, mechanotransductive responses are involved in tenoctye homeostasis, healing, and degeneration. Tenocyte homeostasis is regulated by the production of degradative enzymes (e.g., matrix metalloproteinases [MMPs]) and extracellular proteins (e.g., collagen). Altered mechanical loading promotes changes in mechanosensitive proteins, including integrins and the tenocyte transcription factor, scleraxis, which is important for tenogenesis. Altered mechanical loading also leads to increased production of transforming growth factor beta 1 (TGFbeta‐1). TGFbeta‐1 is a key regulator of differentiation, proliferation, and extracellular matrix production for most cell types, including tenocytes. The production of several other proteins is altered by mechanical loading, including the cytokine IL‐1, cyclooxygenase 2 (COX2), platelet‐derived growth factor (PDGF), and CCN2/CTGF (cell communication network factor 2, formally known as connective tissue growth factor). In this manner, altered mechanical loading can lead to catabolism (via a degradative environment) or anabolism (increased tenocyte biomechanical properties via altered production in the mix of extracellular matrix proteins).
Cartilage
Cartilage is unique in all of the body tissues in that it is typically avascular, aneural, and alymphatic (Tortora & Derrickson, 2010). Because of these properties, injuries and damage to cartilage can be difficult to detect until they are quite severe, and difficult from which to heal. The general features of cartilage are summarized in Table 3.4.
Structure
Cells
Chondrocytes are the prevalent cells of cartilage, with the number per matrix ratio differing with cartilage type. Chondrocytes arise from chondroblasts, which are proliferating cells that originate from mesenchymal cells after exposure to the transcription factor SOX9 [sex determining region Y (SRY)‐box 9]. Chondroblasts produce type II collagen, aggrecan, proteoglycans, and glycosaminoglycans, and therefore, the cartilaginous matrix. They become embedded in individual lacunae within the matrix that they produce (Figure 3.15); once embedded, they become chondrocytes. Chondrocytes then maintain the cartilage matrix throughout life, although the numbers of chondrocytes reduce with age. Joint trauma, inflammation, and stress fractures that extend into the cartilage can lead to chondrocyte damage and severe structural damage of the cartilage (Xiong & O'Brien, 2012).
Table 3.4 Summary of Cells, Extracellular Matrix (ECM), Subtypes, and Function of Cartilage and its Subtypes Under Normal Conditions
| Characteristic | Description |
|---|---|
| Tissue type | Dense pliable connective tissue |
| Cells | Main cell types: Chondrocytes, chondroblastsAdditional cell types: Mesenchymal stem cells (low in number) |
| ECM | Hyaline cartilage: Collagen II (15–20%), water (60–80%), GAGs (e.g., hyaluronic acid)Fibrocartilage: High collagen content, lower water content than hyalineElastic cartilage: High elastin fiber content |
| Subtypes | Hyaline (and its subtype, articular cartilage), fibrocartilage, elastic |
| Function | Hyaline: Protection of bony surfaces, especially at points of movementFibrocartilage: Strength and rigidity, joint support and fusionElastic cartilage: Resilience and pliability |
Extracellular matrix
In general, the extracellular material of each type of cartilage is firm but pliable. Cartilage consists of a dense network of collagen fibers (the type dependent on the subtype of cartilage) and sometimes elastic fibers, each embedded in chondroitin sulfate (a jelly‐like substance). The collagen fibers add great strength to cartilage, while the ability of cartilage to assume its original shape after deformation is due to the chondroitin
