ABSTRACT:The wide range of disease prevalences reported in epidemiological studies of temporomandibular degenerative joint disease reflects the fact that diagnoses are frequently guided by the presence or absence of non-specific signs and symptoms. Treatment is aimed at alleviating the disease symptoms rather than being guided by an understanding of the underlying disease processes. Much of our current understanding of disease processes in the temporomandibular joint is based on the study of other articular joints. Although it is likely that the molecular basis of pathogenesis is similar to that of other joints, additional study of the temporomandibular joint is required due to its unique structure and function. This review summarizes the unique structural and molecular features of the temporomandibular joint and the epidemiology of degenerative temporomandibular joint disease. As is discussed in this review, recent research has provided a better understanding of the molecular basis of degenerative joint disease processes, including insights into: the regulation of cytokine expression and activation, arachidonic acid metabolism, neural contributions to inflammation, mechanisms of extracellular matrix degradation, modulation of cell adhesion in inflammatory states, and the roles of free radicals and heat shock proteins in degenerative joint disease. Finally, the multiple cellular and molecular mechanisms involved in disease initiation and progression, along with factors that may modify the adaptive capacity of the joint, are presented as the basis for the rational design of new and more effective therapy.

The response of human MG-63 osteosarcoma cells to physiological levels of hydrostatic pressure was studied. Cell cultures were subjected to a 20-min, 4-MPa hydrostatic pressure pulse. Adhesion was measured at 20 min and 2 h post-hydrostatic pressure. Morphometric measurements of cell shape and immunofluorescent assays of cytoskeletal and adhesion proteins were done pre- and post-hydrostatic pressure. Pressure-treated cells showed increased adhesion (resistance to deadhesion by trypsinization)-with increased recovery time. Indirect immunofluorescence demonstrated increased heterotypic adhesion receptor at cell-cell interfaces and increased alpha 3, beta 1-integrin at cell-substrate interfaces. Indirect immunofluorescence demonstrated depolymerization of alpha-tubulin, vimentin, and actin during the pressure pulse. Actin reorganization was slower than that of alpha-tubulin and vimentin, with stress filaments not well organized even after 1 h postpressure. The depolymerization of alpha-tubulin, vimentin, and actin observed at relatively low levels of hydrostatic pressure suggests disintegration of the integrin-cytoskeletal attachment complex. The increased resistance of the cells to trypsinization and the increase in both heterotypic adhesion receptor and the alpha 3, beta 1-integrin at cell interfaces suggest that cells compensate for loss of cytoskeletal integrity by increasing attachment to both adjacent cells and the extracellular matrix.

Human osteosarcoma cells, MG-63, were exposed to a hydrostatic pressure shock of 4.0 MPa for 20 min. Changes in subcellular distribution of the cytoskeletal elements and heat shock protein 70 (hsp70) were followed by indirect immunofluorescence and by avidin-biotin-peroxidase protocols. During recovery, total cellular RNA was determined and actin and aldolase mRNA content was followed using reverse transcription-polymerase chain reaction techniques. Hydrostatic pressure caused cell rounding (but not cell death), disruption of microtubules, collapse of intermediate filaments to a perinuclear location, collapse of actin stress fibers into globular aggregates in the cytoplasm, and the formation of several large elongated intranuclear actin inclusions. During recovery, the cells flattened, reorganized microtubules, and redistributed intermediate filaments prior to the reappearance of actin stress fibers. At 20 and 60 min following the initiation of hydrostatic pressure, there was increased anti-hsp 70 staining at the nuclear membrane and concentration of hsp70 in four to six granules in the nucleus. At 120 min following the hydrostatic pressure, hsp70 showed intense staining in the cytoplasm and hsp70-containing granules in the nucleus disappeared. Cellular RNA decreased during the first 120-min posthydrostatic pressure shock and then recovered to near prehydrostatic pressure treatment levels by 240 min. Actin mRNA abundance, in relation to aldolase mRNA abundance, showed the same temporal pattern of initial decrease, followed by increase as did total RNA. Review of the literature indicated that eukaryotic cells respond to heat shock and to hydrostatic pressure by disruption of the cytoskeletal elements and by similar modifications in genetic expression. In this study, the observed responses of MG-63 cells to a 4-MPa hydrostatic pressure shock was like the reported response of mammalian cells to a 43 degrees C heat shock.

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