Musculoskeletal Disorders. Sean Gallagher
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 sulfate. The three primary types of cartilage, namely hyaline (articular) cartilage, fibrocartilage, and elastic cartilage, can be distinguished from each other by the type of fibers within the matrix.
Organization
While the cell types are similar in each type of cartilage, the organization of cells and collagen/elastin fibrils differ extensively between types. The characteristics of each are described in detail next.
Hyaline Cartilage
Structure
Hyaline cartilage is the most abundant type of cartilage (Figure 3.14). It is located at the ends of long bones (where it is called articular cartilage; Figure 3.14a,b), epiphyseal growth plates (Figure. 3.14c,d), ribs (where it is called costal cartilage), and in parts of the larynx, trachea, bronchi, and bronchial tubes. During growth, chondrocytes and hyaline cartilage are also present within the epiphyseal plate, becoming hypertrophic and releasing factors necessary for osteoblast, osteoclast, and endothelial cell invasion needed for bone lengthening (Figure 3.14c,d). Hyaline cartilage contains numerous chondrocytes responsible for manufacturing, secretion, organization, and maintenance of the organic components of the extracellular matrix (Nordin & Frankel, 2012). The ground substance is homogeneous and amorphous and is composed of fine collagen type II fibrils embedded in a concentrated solution of proteoglycans. Specifically, the collagen content of hyaline cartilage ranges from 15 to 20% of the wet weight. The matrix of hyaline cartilage contains three types of glycosaminoglycans (hyaluronic acid, chondroitin sulfate, and keratin sulfate). The chondroitin and keratin sulfates are joined together by a core protein to form a proteoglycan monomer. The proteoglycans account for 4–7% by wet weight (Nordin & Frankel, 2012; Ross, Romrell, & Kaye, 1995). About 80 proteoglycans are associated with each hyaluronic acid molecule in large aggregates reinforced by linking‐type proteins. These aggregates are bound to the thin collagen fibrils by electrostatic interactions and cross‐linking glycoproteins. The remainder of the matrix is composed of water (60–78%), inorganic salts, and small amounts of link proteins, glycoproteins, and lipids. Some of the water is loosely bound, allowing diffusion of small metabolites to the chondrocytes, which is key in this typically avascular tissue.
Figure 3.14 Hyaline cartilage. (a and b) Hyaline cartilage in the articular ends of the distal radius and a carpal bone of the radiocarpal joint. This is a plane‐type joint. The higher power image of panel B shows chondrocytes