TAZ contributes to osteogenic differentiation of periodontal ligament cells under tensile stress

• Published in: Journal of periodontal research Vol. 55; no. 1; pp. 152 - 160
• Main Authors: Wang, Yi, Hu, Bibo, Hu, Rongdang, Tong, Xianqin, Zhang, Menghan, Xu, Chuchu, He, Zhiqi, Zhao, Ya, Deng, Hui
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2020
• Subjects: Actin; Alkaline phosphatase; Bone remodeling; Cell Differentiation; Cells, Cultured; Collagen (type I); Core Binding Factor Alpha 1 Subunit - metabolism; core‐binding factor α1 (Cbfα1); Dentistry; Filaments; Humans; Immunofluorescence; Immunoprecipitation; Kinases; Ligaments; Localization; Mechanical stimuli; Nodules; Orthodontics; Osteoblastogenesis; Osteoblasts; Osteocalcin; Osteogenesis; Periodontal ligament; Periodontal Ligament - cytology; periodontal ligament cells; Protein kinase; Proteins; rho-Associated Kinases - metabolism; Signal Transduction; siRNA; Stress, Mechanical; tensile strain; Trans-Activators - physiology; Transcription; transcriptional co‐activator with PDZ‐binding motif (TAZ); periodontal ligament cells; transcriptional co-activator with PDZ-binding motif (TAZ); tensile strain; osteogenesis; core-binding factor α1 (Cbfα1)
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.12698

Background and objective Bone remodeling during orthodontic treatment is achieved by the osteogenesis of human periodontal ligament cells (PDLCs) subjected to mechanical loadings. Transcriptional co‐activator with PDZ‐binding motif (TAZ) mediates bone remodeling in response to extracellular mechanical signals. This study aims to investigate the role of TAZ in osteogenesis of PDLCs under tensile strain. Materials and methods A uniaxial cyclic tensile stress (CTS) at 12% elongation and 6 cycles/min (5 s on and 5 s off) was applied to PDLCs. The osteogenic differentiation was determined by the protein and gene expressions of osteogenic markers using qRT‐PCR and Western blot, respectively, and further by alkaline phosphatase (ALP) activity and Alizarin Red S staining. The interaction of TAZ with core‐binding factor α1 (Cbfα1) was examined by co‐immunoprecipitation. The immunofluorescence histochemistry was used to examine the nucleus aggregation of TAZ and the reorganization of actin filaments. Moreover, small interfering RNA‐targeting TAZ (TAZsiRNA) was used for TAZ inhibition and Y‐27632 was employed for Ras homologue‐associated coiled‐coil protein kinase (ROCK) signaling blockage. Results CTS clearly stimulated the nucleus accumulation of TAZ and its interaction with Cbfα1. CTS‐induced osteogenesis in PDLCs was significantly abrogated by the infection with TAZsiRNA, as shown by the decreased stained nodules and protein expressions of Cbfα1, collagen type I, osterix, and osteocalcin, along with the inhibition of β‐catenin signaling. Moreover, ROCK inhibition by Y‐27632 hindered TAZ nucleus aggregation and its binding with Cbfα1, which subsequently lead to the decreased osteoblastic differentiation of PDLCs. Conclusions Taken together, we propose that TAZ nucleus localization and its interaction with Cbfα1 are essential for the CTS‐induced osteogenic differentiation in PDLCs. And such TAZ activation by CTS could be mediated by ROCK signaling, indicating the pivot role of ROCK‐TAZ pathway for PDLCs differentiation.