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Orthodontic forces deform the extracellular matrix and activate cells of the paradental tissues, facilitating tooth movement. Discoveries in mechanobiology have illuminated sequential cellular and molecular events, such as signal generation and transduction, cytoskeletal re-organization, gene expression, differentiation, proliferation, synthesis and secretion of specific products, and apoptosis. Orthodontists work in a unique biological environment, wherein applied forces engender remodeling of both mineralized and non-mineralized paradental tissues, including the associated blood vessels and neural elements. This review aims at identifying events that affect the sequence, timing, and significance of factors that determine the nature of the biological response of each paradental tissue to orthodontic force. The results of this literature review emphasize the fact that mechanoresponses and inflammation are both essential for achieving tooth movement clinically. If both are working in concert, orthodontists might be able to accelerate or decelerate tooth movement by adding adjuvant methods, whether physical, chemical, or surgical.

Human periodontal ligament (PDL) fibroblasts, cultured from extracted healthy premolars, and a cloned osteogenic cell line (MC3T3-E1) were used in this study to determine the effect of intermittent pressure on bone resorption. Cells (1 x 10(5] were incubated with BGJb medium in the presence or absence of the following factors: intermittent negative (-30 g/cm2) or positive (30 g/cm2) hydrostatic pressure and interleukin-1 beta (IL-1 beta, 1 ng/mL), for 24 h. Conditioned media (CM) generated from cultures of either cell types were used for prostaglandin E (PGE) assay, bone resorption assay, and assessment of osteoclast (OC)-like cell formation. Unstimulated PDL fibroblasts or MC3T3-E1 cells produced measurable amounts of PGE and bone-resorbing activity as measured by 45Ca released from mouse calvaria and OC-like cells. IL-1 beta-treated cells showed significantly elevated levels of PGE, bone resorption, and OC-like cell formation, as compared with unstimulated cells. Intermittent positive pressure (IPP) alone stimulated PGE production, but the resultant CM did not stimulate bone resorption or OC-like cell formation when IPP was applied to either cell type. The application of IPP, together with IL-1 beta in CM, caused a slight increase in the number of alpha-like cells, as compared with that of IL-1 beta-treated CM in both cell types. On the other hand, direct application of IPP on mouse bone-marrow cultures significantly increased the number of OC-like cells. This effect was additive in combination with either CM from unstimulated cells or exogenous addition of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Mononuclear cell production of cytokines that stimulate fibroblast production of prostaglandin E (PGE) is an important mechanism by which mononuclear cells regulate fibroblast function. The objective of this investigation was to determine the effects of the cytokines interleukin 1 beta (IL-1 beta), interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma), alone or in paired combinations, on PGE production by near-confluent human periodontal ligament (PDL) fibroblasts in vitro. Premolars extracted in the course of orthodontic treatment were used for this study. Fibroblast cultures, free of epithelial cells, were obtained after the fourth subculture by the use of accurately-timed trypsin treatment. Cells in the fourth to sixth passage, incubated in DMEM supplemented with 10% equine serum, were used for these experiments. Cells (1 x 10(5)) were seeded in 12- x -75-mm tissue culture tubes and incubated with various doses of IL-1 beta, IL-1 alpha, TNF-alpha, and IFN-gamma, alone or in specific combinations, for 15 min, two, 12, 24, and 72 h. PGE concentrations in the media were measured by radio-immunoassay. The results showed that human PDL fibroblasts responded to the administration of cytokines by an elevation in the synthesis of PGE in a dose- and time-related fashion. The increase in PGE production was inhibited by the addition of indomethacin. The interactions between these cytokines varied in degree, depending on the particular combinations of cytokines. In addition, the administration of cytokine combinations was found to be additive, synergistic, subtractive, or suppressive on the production of PGE by PDL fibroblasts, depending on the duration of incubation. These experiments demonstrate the importance of the consideration of the interplay between cytokines produced by mononuclear cells on the mechanisms that regulate the functions of PDL fibroblasts.

Cyclic adenosine 3',5'-monophosphate (cAMP) concentrations and cellular distribution were studied in dental and periodontal tissues during tooth eruption in kittens. Although the mean levels of cAMP around developing teeth were similar in all the tissue samples, there were marked differences in cAMP stainability of tissues apical and occlusal to the erupting teeth.