Читать книгу Biological Mechanisms of Tooth Movement - Группа авторов - Страница 44

Cell–cell interactions allow cells to communicate with each other in response to changes in their microenvironment. These interactions can be stable through intercellular junctions, such as tight junctions, desmosomes, and gap junctions. They can also be variable, through the binding of soluble proteins secreted by one cell to receptor proteins on another cell. Such interactions allow cells to communicate with adjacent cells (autocrine actions), nearby cells (paracrine actions) (Tse and Wong, 2019), and even distant cells via the vascular system (endocrine actions). The latter actions are dealing with hormonal regulation.

For OTM, autocrine and paracrine interactions are essential. Secreted regulatory factors can bind to specific receptors on the target cell. These receptors are transmembrane structures containing proteins, carbohydrates, and lipids that project into the extracellular compartment. The binding of the signaling molecule to the receptor induces conformational changes in the receptor which, in turn, elicits a response in the corresponding cell. These responses include changes in cytoskeletal structure and subsequently change gene expression (McGeachie and Tennant, 1997; Meikle, 2006; Jiang et al., 2015).

Two groups of local regulatory proteins are distinguished, namely growth factors and cytokines. The growth factors mainly affect cellular growth, proliferation, differentiation, and maturation, while the cytokines are primarily associated with hematopoietic and immunological processes. The latter can act as proinflammatory or as anti‐inflammatory mediators, and they can enhance cellular immune and antibody responses. The distinction between growth factors and cytokines is not very strict, since some cytokines can also act as growth factors and stimulate or inhibit cell growth and differentiation.

Growth factors and cytokines are grouped in several families. The most important factors involved in bone remodeling and thus in OTM belong to the transforming growth factor‐β (TGFβ) super family including TGFβs and bone morphogenetic proteins (BMPs), epidermal growth factors (EGF) including EGF and transforming growth factor‐α (TGFα), fibroblast growth factors (FGFs), insulin‐like growth factors (IGFs), vascular endothelial growth factors (VEGFs), tumor necrosis factors (TNFs), and colony‐stimulating factors (CSFs) (Roodman, 1993; McGeachie and Tennant, 1997; Hadjidakis and Androulakis, 2006; Jiang et al., 2015).

Another group of local regulatory molecules consists of the eicosanoids. They synthetize from arachidonic acid that is released from cell membranes through phospholipase A2. Free arachidonic acid can be converted to bioactive eicosanoids through the so‐called arachidonic cascade, chains of enzymatic reactions, resulting in different subgroups of signaling molecules such as prostacyclines, thromboxanes, lipoxanes, and leukotrienes. For OTM, the most important subgroup is formed by the prostaglandins, which are formed through the activity of cyclooxygenases (COX1 and COX2) and prostaglandin synthase (Harizi et al., 2008; Xia et al., 2016; Vansant et al., 2018). Prostaglandins are synthetized within a large variety of cells. After exocytose they can bind to prostaglandin receptors on different target cells, in which a wide variety of effects can be induced (Binderman et al., 1988; Mundy, 1993; Hadjidakis and Androulakis, 2006)