Human Parathyroid Hormone Analog (3-34/29-34) promotes wound re-epithelialization through inducing keratinocyte migration and epithelial-mesenchymal transition via PTHR1-PI3K/AKT activation.

BACKGROUND: Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3-34/29-34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1-34), and evaluated its effect on skin wound re-epithelialization. METHODS: CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial-mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1's role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models. RESULTS: In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation. CONCLUSION: Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation. Video Abstract.

[Comparative evaluation of the tiled abutment teeth restored with or without fixed bridge on stress distribution by anisotropic finite element method].

OBJECTIVE: To compare the tilted abutment teeth restored with or without fixed bridge on stress distribution by anisotropic finite element method when the vertical and the oblique loads are simulated. METHODS: Three-dimensional finite element model was constructed by using SCT image reconstruction technique, self-programming and ANSYS software with the anisotropic elasticity data. The static loads were simulated according to the restored and unrestored situation. The stress distribution and stress level of the second molar was recorded. RESULTS: When the vertical static load was simulated, the stress distribution of the tilted abutment teeth was much improved. Tensile stresses appeared dominantly on the mesial apex of the second molar (31.0 Mpa) before restoration and on the distal apex of the second molar (20.2 Mpa) after restoration. When the oblique load was simulated, the stress distribution changed a little. CONCLUSION: The stress distribution of the tilted abutment can be improved by restorative techniques with the use of fixed bridge; however, the clinician should lower the height of the cusp to reduce the oblique load of the abutment.

[Analysis of the movement of long axis and the distribution of principal stress in abutment tooth retained by conical telescope].

OBJECTIVE: To study the movement of long axis and the distribution of principal stress in the abutment teeth in removable partial denture which is retained by use of conical telescope. METHODS: An ideal three dimensional finite element model was constructed by using SCT image reconstruction technique, self-programming and ANSYS software. The static loads were applied. The displacement of the long axis and the distribution of the principal stress in the abutment teeth was analyzed. RESULTS: There is no statistic difference of displacenat and stress distribution among different three-dimensional finite element models. Generally, the abutment teeth move along the long axis itself. Similar stress distribution was observed in each three-dimensional finite element model. The maximal principal compressive stress was observed at the distal cervix of the second premolar. CONCLUSION: The abutment teeth can be well protected by use of conical telescope.

The relationship between IL-1 gene polymorphism and marginal bone loss around dental implants.

PURPOSE: Early marginal bone loss around dental implants has been found during the bone healing period before stage II surgery despite a lack of apparent cause, and the etiology of this bone loss is unclear. This study was designed to investigate whether interleukin-1 gene polymorphism is associated with the marginal bone loss around the implants before stage II. MATERIALS AND METHODS: One hundred forty-three implants were placed in 59 patients. The patients were divided into 2 groups: 1) test group: with 1 or more marginal bone loss greater than 0.5 mm; and 2) control group: with marginal bone resorption less than 0.5 mm. Polymorphisms of the IL-1alpha and IL-1beta genes (IL-1A-889, IL-1B-511, and IL-1B+3954) were detected by restriction fragment length polymorphism using Ncol, AvaI, and TaqI digestion after polymerase chain reactions. RESULTS: The frequency of IL-1B-511 II/II was significantly higher among patients in early marginal bone loss (+) group than those in early marginal bone loss (-) group (P < .05). Multiple logistic regressions showed the OR of the II/II versus the I/I+I/II of the IL-1B-511 genotype was 3.933 between the 2 groups. The difference was statistically significant (P < .05). There was no significant difference between the other risk factors. CONCLUSION: These results suggest that the IL-1B-511 II/II genotype in individuals is associated with early marginal bone loss around implants.