Tendon and Mast Cells: History
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Subjects: Cell Biology
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Understanding the structure and composition of tendon is crucial to understand the human tendon disorders. It also important to understand the tendon healing and inflammation following tendon tissue injury. In this entry, we discuss tendon basic composition and mast cells involvement with their molecular function.

  • Tendon, Tenocytes, Collagen, Mast cells

Tendon is a crucial component of the musculoskeletal system that connects muscle to bone and transmits force for the movement [11,12]. Tendon is a soft connective tissue and is predominately composed of water, which makes up 55–70% of the total tendon weight. The other major component of tendon is collagen, which represents about 60–85% of the dry weight of tendon [13]. In tendon architecture, fibrillar arrangement of triple-helical type I collagen molecules generates collagen fibers, which then combine to form fascicles and, ultimately, the tendon tissue. The type I collagen molecule contains two identical α1 chains and one α2 chain, which are encoded by col1a1 and col1a2, respectively [12]. The collagen fibrils are the fundamental force-transmitting element of tendon tissue, and are tightly arranged within the extracellular matrix. Type I collagen and associated extracellular matrix components are produced by tenocytes, which are fibroblast-like cells found between collagen fibers and in the surrounding of the endotenon [14]. Tendons also contain other cell types such as chondrocytes, vascular cells, synovial cells, tendon stem cells (TSCs) including mast cells. Tendon mast cells are in the normal state resident locally in the tendon tissue or in the loose connective tissue close to the paratenon, muscle–tendon junction, or bone–tendon junction [5]. However, during the tendon healing process, they may migrate to the injured site (tendon proper) following inflammation and nerve ingrowth [5,72]. In addition to tendon cells and collagen, other molecules like elastin and proteoglycans are also integral parts of the tendon [15]. There are two main markers of collagen metabolism: procollagen type III N-terminal propeptide (PIIINP) and procollagen type I N-terminal propeptide (PINP). Both have been used as early prediction markers for healing tendon and bone [16]. Procollagen type I and III are essential building blocks in all types of connective tissues, and PINP and PIIINP have been utilized as biomarkers to assess collagen metabolism in intact human Achilles tendons exposed to exercise and growth factor stimulation [16]. 

Mast cells are highly granulated hematopoietic cells derived from the bone marrow. They circulate in the blood as immature progenitor cells, after which they home into tissues where they mature under the influence of local growth factors such as stem cell factor [44,45,46,47]. In their mature state, mast cells are characterized by a remarkably high content of electron-dense secretory granules. These contain a plethora of preformed mediators, including serglycin proteoglycans, proteases (e.g., chymase, tryptase, and carboxypeptidase A3), biogenic amines (histamine, serotonin, and dopamine), lysosomal hydrolases, growth factors, and certain cytokines (e.g., tumor necrosis factor-α (TNF-α)) [48,49,50]. When mast cells are activated, they typically respond by degranulation, whereby the preformed mediators are released to the extracellular space. Mast cell activation also leads to the de novo synthesis of a range of other mediators, including additional growth factors, cytokines, chemokines, as well as various lipid-derived mediators such as platelet-activating factor, prostaglandins, and leukotrienes (see Figure 2 ) [50]. Mast cells can be activated through a variety of mechanisms. Of these, crosslinking of IgE molecules bound to their high affinity receptors (FcεRI) on the mast cell surface represents the classical mode of mast cell activation. However, mast cells can be activated through several alternative pathways, including complement, engagement of toll-like receptors, and ligation of Mas-related G-protein coupled receptor member X2 (MRGPRX2)[2,51,52,53,54].

Mast cells have been suggested to have a number of beneficial functions, e.g., in the context of bacterial and parasite infection, as well as in wound healing and in the defense against various toxins [55,56,57,58,59]. Conversely, mast cells have also been implicated as detrimental players in several pathological settings. Most notably, mast cells are strongly implicated in allergic disorders but there is also evidence supporting the contribution of mast cells in various autoimmune diseases, fibrosis, cancer, skin inflammation, and metabolic disorders [48,60,61,62,63,64,65,66,67]. In addition, there is emerging evidence suggesting that mast cells potentially could be involved in conditions associated with neurogenic inflammation [51,68,69,70,71]. In support of a functional nerve:mast cell communication, mast cells are frequently found in close association with nerve endings [69,70,71]. However, the mechanisms by which mast cells could respond to nerve signaling have been mostly elusive.

 

This entry is adapted from the peer-reviewed paper 10.3390/cells9051134

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