Читать книгу Biological Mechanisms of Tooth Movement - Группа авторов - Страница 59

According to Krishnan and Davidovitch (2006a), while paradental tissues become progressively strained by applied forces, their cells are continuously subjected to other first messengers, derived from cells of the immune and nervous systems. The binding of these signal molecules to cell membrane receptors leads to enzymatic conversion of cytoplasmic ATP and GTP into adenosine 3´,5´‐monophosphate (cyclic AMP [cAMP]), and guanosine 3´,5´‐monophosphate (cyclic GMP [cGMP]), respectively. These latter molecules are known as intracellular second messengers. Immunohistochemical staining during OTM in cats showed high concentrations of these molecules in the strained paradental tissues (Davidovitch et al., 1988).

Internal cellular signaling systems are those that translate many external stimuli into a narrow range of internal signals or second messengers (Sandy et al., 1993). Cyclic AMP and cGMP are two second messengers associated with bone remodeling. Bone cells, in response to hormonal and mechanical stimuli, produce cAMP in vivo and in vitro. Alterations in cAMP levels have been associated with synthesis of polyamines, nucleic acids, and proteins, and with secretion of cellular products. The action of cAMP is mediated through phosphorylation of specific substrate proteins by its dependent protein kinases. In contrast to this role, cGMP is considered an intracellular regulator of both endocrine and nonendocrine mechanisms (Davidovitch, 1995). The action of cGMP is mediated through specific substrate proteins by cGMP‐dependent protein kinases. This signaling molecule plays a key role in the synthesis of nucleic acids and proteins, as well as secretion of cellular products.

According to Meikle (2006), the second messenger system classically associated with mechanical force transduction is cAMP. The first evidence for the involvement of the cAMP pathway in mechanical signal transduction was provided independently by Rodan et al. (1975), and by Davidovitch and Shanfeld (1975). Rodan et al. (1975) showed that a compressive force of 60 g/cm² applied to 16‐day‐old chick tibia in vitro inhibited the accumulation of cAMP in the epiphyses, as well as in cells isolated from the proliferative zone of the growth plate. The effect was mediated by an enhanced uptake of Ca²⁺ which inhibited membrane‐associated adenyl cyclase activity.

Davidovitch and Shanfeld (1975) sampled alveolar bone from compression and tension sites surrounding orthodontically tipped canines in cats. They found that cAMP levels initially decreased, followed by an increase after 1–2 days, which remained elevated to the end of the experimental period of 28 days. They suggested that the initial decrease at the compression sites was due to necrosis of PDL cells, and at the tension sites to a rapid increase in the cell population; the elevation in cAMP observed 2 weeks after the initiation of treatment was probably a reflection of increased bone remodeling activity. Subsequently, Davidovitch et al. (1976), in a study on the cellular localization of cAMP in the same model, found an increase in the number of cAMP‐positive cells in areas of the PDL where bone resorption or deposition subsequently occurred. Osteocytes in the adjacent alveolar bone, however, appeared to be relatively unaffected by the mechanical force.