The Regulatory Role of ADAM28 in Tooth Development

Objectives: ADAM28 gene was screened from the patients with congenital hypoplasia of tooth root (CHTR).According to clinical feature CHTR was separated into dentin developmental anomaly of tooth root, cementum developmental defect of root, root paramorphia, and root adhesive organ dysplasia.Nowadays, no therapy of CHTR has been detected in the world, and its potential mechanisms are unknown.ADAM28 has been regarded as one of the possible virulence genes for CHTR.The objective of this study was to outline the influence of ADAM28 on proliferation, differentiation, and apoptosis of human odontogenic mesenchymal cells and the regulatory role of ADAM28 in tooth development and action mechanism.Methods: Immunological, cell biological and molecular biological techniques were used for detecting the effects of ADAM28 on odontogenic mesenchymal cells. Results: ADAM28 may actively participate in tooth root development process as a major regulator of proliferation, differentiation, and apoptosis of human odontogenic mesenchymal cells by interacting with Notch signal pathway. The action mechanism might be that ADAM28 release IGF-1 and lead to activation of IGF signaling pathway, and further accelerate cell proliferation. ADAM28 AS-ODN and shRNA interference vector might inhibit catalytic cracking of metalloproteinase and disintegrin domain, and suppress the promoting cell proliferation of EGF-like domain, block Notch signal transmission and participate in negative regulation of apoptosis.Conclusions: ADAM28 metalloproteinase inhibitor could be an effective therapeutic target against CHTR.ADAM28 inhibition can reduce inflammation due to diminished IGFBP-3 cleavage and TNF- shedding, and may be served as a means of treating CHTR.