Understanding the pattern and molecular mechanisms of tooth, maxilla and mandible development is the prerequisite for studying their regeneration. Tooth development can be divided into three stages: bud-bell stage, tooth crown development stage and tooth root development stage. During these processes, key genes show spatial and temporal expression pattern. Tooth development is a complex process involving interactions between dental epithelium and mesenchyme, precise regulations of enamel knots in cusp patterning, as well as successful eruption into the oral cavity under proper biomechanical stress and signaling transductions. The development of tooth, maxilla and mandible, all of which originate from the first branchial arch, is independent and regulates each other to form a whole during development. Any developmental defects of them will ultimately cause defects to the others. In this paper, we briefly reviewed the development of tooth, maxilla and mandible, proposed that the homeostasis of microenvironment is critical for their development. Moreover, we reviewed the role of Meckel’s cartilage, a special structure and signaling mechanism during mandible development. At last, we proposed an integrated development model of tooth, maxilla and mandible. We also hope that the regeneration of fully functional tooth, maxilla and mandible in human can be achieved based on fundamental knowledge we have gained so far.

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Colitis ; Exosomes ; Humans ; Periodontitis/therapy* ; Periodontium ; T-Lymphocytes, Regulatory ; Th17 Cells