RESUMO
The transforming growth factor ß (TGFß) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFß signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFß receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFß-related diseases.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Polpa Dentária , Dentina , Receptor do Fator de Crescimento Transformador beta Tipo II , Transdução de Sinais , Animais , Polpa Dentária/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/genética , Dentina/metabolismo , Camundongos Knockout , Odontoblastos/metabolismoRESUMO
INTRODUCTION: In this study, we aimed to compare the incidence of new demineralized lesions and bond failures between 2 groups of participants wearing fixed orthodontic appliances bonded with either light-cured resin-modified glass ionomer cement or light-cured composite. METHODS: This trial was a multicenter (6 centers: 2 teaching hospitals, 4 specialist orthodontic practices), single-blinded, randomized controlled trial with 2 parallel groups. Patients aged 11 years or older, in the permanent dentition, and about to start fixed orthodontic treatment in these 6 centers were randomly allocated to have either resin-modified glass ionomer cement or light-cured composite for bonding brackets, forward of the first molars. Pretreatment and day-of-debond digital photographic images were taken of the teeth and assessed by up to 5 clinical and 3 lay assessors for the presence or absence of new demineralized lesions and the esthetic impact. The assessors were masked as to group allocation. RESULTS: We randomized 210 participants, and 197 completed the trial. There were 173 with complete before-and after-digital images of the teeth. The incidence of new demineralized lesions was 24%; but when the esthetic impact was taken into account, this was considerably lower (9%). There was no statistically significant difference between the bracket adhesives in the numbers with at least 1 new demineralized lesion (risk ratio,1.25; 95% confidence interval, 0.74-2.13; P = 0.403) or first-time bracket failure (risk ratio,0.88; 95% confidence interval, 0.67-1.16; P = 0.35). There were no adverse effects. CONCLUSIONS: There is no evidence that the use of resin modified glass ionomer cement over light-cured composite for bonding brackets reduces the incidence of new demineralized lesions or bond failures. There might be other reasons for using resin modified glass ionomer cement. REGISTRATION: This trial was registered at ClinicalTrials.govNCT01925924. PROTOCOL: The protocol is available from the corresponding author on request.