Abstract
A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.
Highlights
IntroductionI (DD-I, OMIM: 125400) is a rare, autosomaldominant, heritable, non-syndromic disorder characterized by obliterated pulp chambers, diminutive roots, and severe hypermobility of teeth.[1,2,3,4] This is often combined with frequent periapical radiolucencies in apparently sound teeth, both in the deciduous and permanent dentitions, with an estimated incidence of 1/100 000.5–7 dentin dysplasia type I (DD-I) increases the risk of early tooth loss and causes functional and esthetic disturbances
1234567890();,: INTRODUCTION Dentin dysplasia type I (DD-I, OMIM: 125400) is a rare, autosomaldominant, heritable, non-syndromic disorder characterized by obliterated pulp chambers, diminutive roots, and severe hypermobility of teeth.[1,2,3,4]
This is often combined with frequent periapical radiolucencies in apparently sound teeth, both in the deciduous and permanent dentitions, with an estimated incidence of 1/100 000.5–7 dentin dysplasia type I (DD-I) increases the risk of early tooth loss and causes functional and esthetic disturbances
Summary
I (DD-I, OMIM: 125400) is a rare, autosomaldominant, heritable, non-syndromic disorder characterized by obliterated pulp chambers, diminutive roots, and severe hypermobility of teeth.[1,2,3,4] This is often combined with frequent periapical radiolucencies in apparently sound teeth, both in the deciduous and permanent dentitions, with an estimated incidence of 1/100 000.5–7 DD-I increases the risk of early tooth loss and causes functional and esthetic disturbances. The genetic defects underlying DD-I were subsequently identified by genetic screening in affected families. Gene mutations in SMOC2, VPS4B, and SSUH2 in three affected families from different countries have been identified, which strongly suggests that this disease is genetically heterogeneous.[4,8,9,10] Despite major advancements in knowledge regarding molecular and cellular involvement in DD-I, the pathogenesis of this dysplasia remains undefined
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