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Expression of thymosin beta-4 in human periodontal ligament cells and mouse periodontal tissue and its role in osteoblastic/cementoblastic differentiation.

Lee, Sang-Im; Lee, Deok-Won; Yun, Hyung-Mun; Cha, Hee-Jae; Bae, Cheol-Hyeon; Cho, Eui-Sic; Kim, Eun-Cheol.
Differentiation; 90(1-3): 16-26, 2015 Jul-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26361868
A recent report showed that thymosin beta-4 (Tß4) is expressed during the development of tooth germ, but its effect on osteoblastic/cementoblastic differentiation is a controversial topic. Furthermore, the precise expression and function of Tß4 in periodontal tissue remains unclear. Therefore, the purpose of this study was to investigate the immunolocalization of Tß4 in the developing periodontium of mouse, the function of Tß4 in osteoblastic/cementoblastic differentiation, and the underlying mechanism regulating periodontal regeneration in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. Tß4 expression was observed in differentiating hPDLCs, osteoblasts of the periodontium during development, as well as in mature tissue. Higher Tß4 expression was observed in hPDLCs than in cementoblasts and osteoblasts in the developing periodontium. The expression of Tß4 mRNA and protein gradually increased during PDL cell differentiation. The downregulation of Tß4 expression by Tß4 siRNA transfection inhibited osteoblastic differentiation by decreasing calcium nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. In contrast, Tß4 activation using a Tß4 peptide, promoted these processes by activation of Akt, p38, ERK MAPKs, and the NF-κB pathway. The expression of nuclear NFATc1 was upregulated by Tß4 peptide in hPDLCs. Inhibition of the calcineurin/NFATc1 pathway by cyclosporin A and FK506, attenuated Tß4-induced osteoblastic differentiation and activation of Wnt-related genes, as well as nuclear ß-catenin in hPDLCs. In conclusion, this study demonstrates, for the first time, that Tß4 is expressed in developing periodontal tissue and that its expression is associated with osteoblastic/cementoblastic differentiation. These results suggests that Tß4 is a potential therapeutic target for periodontal regeneration or bone disease.
Selo DaSilva