Conclusions
TEAD1 is a novel mechano-responsive gene and plays an important role in force-induced osteoclastogenesis, which is dependent, as least partially, on transcriptional regulation of OPG.
Methods
We first analyzed the correlation between several transcription factors and OPG expression in human periodontal ligament cells (PDLCs). Then dynamic expression changes of TEAD1 with force application were analyzed due to its high correlation with OPG. Loss-of-function experiments were performed to demonstrate the role of TEAD1 in regulation of RANKL/OPG, as well as osteoclastogenesis by tartrate-resistant acid phosphatase (TRAP) staining. Combination of bioinformatics analyzes and chromatin immunoprecipitation assay was utilized to investigate occupancy of TEAD1 on the enhancer elements of OPG and the dynamic change in response to force stimuli. Involvement of Hippo signaling in regulation of OPG was further demonstrated by pharmacologic inhibitors of several components.
Objective
This study aims to investigate the responsiveness of transcription factor TEA domain family member 1 (TEAD1) to mechanical force and its impact on osteoclastogenesis as well as expression of Osteoprotegerin (OPG), an inhibitor for osteoclastogenesis playing crucial roles in mechanical stress-induced bone remodeling and orthodontic tooth movement (OTM).
Results
Expression of TEAD1 highly correlates with that of OPG and decreases in response to mechanical force in human PDLCs. Knockdown of TEAD1 downregulates expression of OPG and promotes osteoclast differentiation. Mechanical force induced decreased binding of TEAD1 on an enhancer element ˜22 kilobases upstream of OPG promoter. OPG was also affected by pharmaceutical disruption of Hippo signaling pathway. Conclusions: TEAD1 is a novel mechano-responsive gene and plays an important role in force-induced osteoclastogenesis, which is dependent, as least partially, on transcriptional regulation of OPG.