Title: 1911 - RUNX2 Mutation Disturbs Bone Remodeling Activity in Cleidocranial Dysplasia
Xiangyu Sun (Presenter)
Peking University School and Hospital of Stomatology
Xiaozhe Wang, Peking University School and Hospital of Stomatology
Yang Liu, Peking University School and Hospital of Stomatology
Chao Yuan, Peking University School and Hospital of Stomatology
peiyuan tong, Peking University School and Hospital of Stomatology
Xianli Zhang, Peking University School and Hospital of Stomatology
Chenying Zhang, Peking University School and Hospital of Stomatology
Shuguo Zheng, Peking University School and Hospital of Stomatology
Objectives: To investigate the impact of Runt-related Transcription Factor-2 gene (RUNX2) mutation on bone remodeling activity of dental follicle cells (DFCs) during tooth eruption in patients with cleidocranial dysplasia (CCD).
Methods: Primary dental follicle cells (DFCs) from the CCD patient and normal controls were collected. After osteogenic induction, Alkaline phosphatase (ALP) activity and the ability of DFCs to form mineralized nodules were tested, while expression of osteogenic-related genes was detected. The effect of RUNX2 mutation on osteoclastogenesis was further explored using a co-culture system composed of DFCs and peripheral blood mononuclear cells (PBMCs) by detecting the formation of tartrate-resistant acid phosphatase-positive (TRAP) multinucleated cells and the expression of osteoclast-associated genes at the molecular and the protein level.
Results: This CCD patient had a missense mutation (c. 557G>C, p. R186T) in RUNX2 gene. Our present study found that ALP activity and mineralizing ability of DFCs were severely interfered by the mutation. The expression of osteogenic-related genes, the formation of TRAP multinucleated cells, and the expression of osteoclast-associated genes were all reduced. RANKL/RANK/OPG signaling pathway was found to be disturbed potentially due to the RUNX2 mutation.
Conclusions: RUNX2 mutation disturbs regulating function of DFCs on the differentiation of osteoblasts and osteoclasts, thereby interferes with bone formation and bone resorption which participate in bone remodeling during tooth formation and eruption. These effects may play an important role in the impaired tooth eruption procedure found in CCD patients.
This abstract is based on research that was funded entirely or partially by an outside source:
The National Natural Science Foundation of China (grant number 81070815)
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE