The ability of cells to sense and respond to physical stress is required for tissue homeostasis and normal development. In muscle, bone, tendon, periodontium, and the cardiovascular system, applied forces of physiological magnitude regulate cellular processes that are critical for normal tissue and organ functions, such as differentiation, proliferation, and migration (1). The periodontal ligament (PDL) 3 is a connective tissue interposed between the roots of teeth and the inner wall of the tooth-supporting bone (alveolar bone) socket. The PDL constitutively and iatrogenically receives mechanical stress, such as occlusal pressure and orthodontic forces, which have effects on the homeostasis of the PDL (2). Proper mechanical stress on teeth induces not only the proliferation and differentiation of PDL cells into osteoblasts and cementoblasts but also the synthesis and degradation of extracellular matrix (ECM) molecules (3). For example, during orthodontic tooth movement, two types of sites (tension sites and pressure sites) arise around the tooth through the orthodontic force. At the tension sites, the PDL is stretched, and the expressions of bone-related genes, such as osteocalcin (4) and bone sialoprotein (5), are up-regulated, such that bone formation is finally induced on the alveolar bone facing the tooth root (6). On the other hand, at the pressure sites, the PDL is compressed, and osteoclasts are activated. Consequently, resorption of the alveolar bone is induced. An orchestrated balance between bone formation and resorption controls tooth movement (7). In contrast, elimination of mechanical stress on teeth is known to cause atrophy of the PDL in vivo (8). Kaneko et al. (9) reported that loss of occlusal function by extraction of the antagonistic upper molars of rats caused atrophic changes in the PDL of the lower molars, such as narrowing of the space, disorientation of collagen fibers, and decreases in proteoglycans. These findings indicate that mechanical stress on teeth affects the remodeling of the PDL, cementum, and alveolar bone. Thus, it is important to clarify the physiological functions of mechanical stress on the PDL.To clarify the molecular basis of the mechanical stress-regulated PDL functions, we analyzed the gene expression profile of human PDL cells receiving tensile mechanical stress in vitro. Interestingly, an oligo-DNA chip analysis identified two glutamate signaling-associated genes, HOMER1 (homer homolog 1) and GRIN3A (glutamate receptor ionotropic N-methyl-D-aspartate 3A), among the up-regulated genes. L-Glutamate is the most abundant amino acid in the central nervous system and plays important roles in neurotransmission (10

Watanabe et al. report that, contrary to the prevailing paradigm, there are unique cellular requirements for B7 and CD40 expression in primary GC responses. B7 is required on DCs but not on B cells, whereas CD40 is required on B cells but not on DCs for generation of Tfh cells, GC B cells, and high-affinity class-switched antibody production.

PLAP-1/asporin is an extracellular matrix protein that is predominantly expressed in the human periodontal ligament (PDL) and has an aspartic acid (D) repeat polymorphism in its N-terminal region. In this study, we hypothesized that the D repeat polymorphism of PLAP-1/asporin may affect the physiological functions of periodontal ligaments. We established periodontal ligament cell lines transfected with the D13- or D14-PLAP-1 gene. Alkaline phosphatase staining and alizarin red staining revealed that the cytodifferentiation of the D14-PLAP-1-expressing PDL cells was more repressed compared with that of the D13-PLAP-1-expressing cells. Furthermore, the D14-PLAP-1-expressing cells inhibited BMP-2-induced cytodifferentiation more strongly than did the D13-PLAP-1-expressing cells. Western blotting analysis and luciferase assay revealed that D14-PLAP-1 suppressed BMP-2 signal transduction more efficiently than did D13-PLAP-1, and co-immunoprecipitation demonstrated the stronger affinity of the D14-PLAP-1 protein to BMP-2 compared with the D13-PLAP-1 protein. Analysis of these data suggests that the D repeat polymorphism of PLAP-1/asporin has a significant influence on the functions of PDL cells.

Thymic development requires bidirectional interaction or cross-talk between developing T cells and thymic stromal cells, a relationship that has been best characterized for the interaction between thymocytes and thymic epithelial cells (TECs). We have characterized here the requirement for similar cross-talk in the maintenance and function of thymic B cells, another population that plays a role in selection of developing thymic T cells. We found that maintenance of thymic B cells is strongly dependent upon the presence of mature single positive (SP) thymocytes and on the interactions of these T cells with specific antigen ligand. Maintenance of thymic B cell number is strongly dependent upon B cell-autonomous expression of CD40, but not MHCII, indicating that direct engagement of CD40 on thymic B cells is necessary to support their maintenance and proliferation. Thymic B cells can mediate negative selection of superantigen-specific self-reactive SP thymocytes, and we show that CD40 expression on B cells is critical for this negative selection. Cross-talk with thymic T cells is thus required to support the thymic B cell population through a pathway that requires cell-autonomous expression of CD40, and that reciprocally functions in negative selection of autoreactive T cells.