Loss of PA28γ exacerbates imbalanced differentiation of bone marrow stromal cells during bone formation and bone healing in mice.

Proteasome activator subunit 3 (PA28γ) is a member of the proteasome activator family, which mainly regulates the degradation and stability of proteins. Studies have shown that it plays crucial roles in lipid formation, stemness maintenance, and blood vessel formation. However, few studies have clarified the association between PA28γ and bone diseases. Herein, we identified PA28γ as a previously unknown regulator of bone homeostasis that coordinates bone formation and lipid accumulation. PA28γ-knockout mice presented with the characteristics of low bone mass and accumulation of lipids. Suppressed expression of PA28γ restrained the osteogenic differentiation and enhanced the adipogenic differentiation of bone marrow stromal cells (BMSCs). Overexpression of PA28γ promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs. Mechanistically, PA28γ interacted with Wnt5α, and the two interactors appeared to be positively correlated. PA28γ mainly activated the downstream Wnt/ß-catenin signaling pathway, which affects BMSCs differentiation homeostasis. Deletion of Wnt5α significantly delayed the promotion of osteogenic differentiation and partially alleviated the inhibitory effect of adipogenic differentiation of BMSCs in the PA28γ-overexpressing group. Furthermore, we demonstrated that PA28γ-knockout mice had an inhibited rate of bone healing in a drill-hole femoral bone defect model in vivo. Therefore, our results confirm the effects of PA28γ on bone formation and bone defect repair, indicating that PA28γ mainly interacts with Wnt5α to activate the Wnt/ß-catenin signaling pathway regulating BMSCs differentiation homeostasis. Our results reveal the function of PA28γ in bone diseases and provide a new theoretical basis for expanding the treatment of bone diseases.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Clinical accuracy of partially guided implant placement in edentulous patients: A computed tomography-based retrospective study.

OBJECTIVES: This retrospective study was intended to evaluate the clinical accuracy of partially guided template in guiding implant placement in edentulous patients. METHODS: A total of 120 implants were placed in 24 patients with at least one completely edentulous arch with a partially guided system. Based on CBCT data, a repeatable method was used to measure linear and angular deviations of implants at 3D level in Mimics medical software. The influence of supporting tissue and implant region on the accuracy was assessed, followed by the evaluation of direction of linear deviations in biologically vital areas. RESULTS: Linear deviations of all implants were 1.91 ± 0.68 mm, 1.47 ± 0.68 mm, and 1.02 ± 0.69 mm at apical, apical lateral, and apical vertical levels. When at the cervical, cervical lateral, and cervical vertical levels, the linear deviations were 1.53 ± 0.65 mm, 0.98 ± 0.53 mm, and 1.01 ± 0.69 mm, respectively. Angular deviation of all implants was 7.14 ± 3.41°. Implants guided by mucosa + tooth-supported templates showed higher linear deviations at apical vertical level (1.21 ± 0.72 mm vs. 0.86 ± 0.63 mm, p < .05) and cervical vertical level (1.18 ± 0.72 mm vs. 0.87 ± 0.63 mm, p < .05) than mucosa-supported templates, and implants in maxilla were found higher angular deviation than mandible (7.89 ± 3.61° vs. 6.29 ± 2.97°, p < .05). CONCLUSIONS: The partially guided template served as clinically viable surgical assistance in implant placement in edentulous patients. When using mucosa + tooth-supported template or placing implants in maxilla, more caution was required, especially in biologically vital areas.

Dental Reimplantation Treatment and Clinical Care for Patients with Previous Implant Failure-A Retrospective Study.

(1) Objectives: This study evaluated the clinical outcomes of dental implants placed in previously failed sites and discussed the risk factors that mattered in reimplantation. (2) Methods: All the cases by one specific implantologist during his first five years of clinical practice were screened, with a focus on those who received reimplantation. The clinical outcomes were assessed, including the implant survival, peri-implant health, and patients' satisfaction. (3) Results: 28 patients (31 implants) were recorded as failures from 847 patients (1269 implants), with a 2.4% overall failure rate at the implant level, of whom 19 patients (21 implants) received reimplantation treatment. After a mean follow-up of 33.7 ± 10.1 months (95% CI 29.1-38.3 months), 20 implants remained functional, but 1 implant revealed a secondary early failure, indicating a 95.2% overall survival rate. The mean probing depth (PD), modified sulcus bleeding index (mSBI), and marginal bone loss (MBL) of the surviving reinserted implants were 2.7 ± 0.6 mm (95% CI 2.5-3.0 mm), 0.7 ± 0.5 (95% CI 0.5-1.0), and 0.5 ± 0.6 mm (95% CI 0.3-0.8 mm), respectively. Embedded healing occurred more frequently in the reinserted implants than in the primary implants (p = 0.052). The patients' satisfaction suffered from implant failure, but a successful reimplantation could reverse it with close doctor-patient communication. (4) Conclusions: Reimplantation treatment was recommended, based on a thorough evaluation and consideration of the risk factors combined with effective communication with the patients.

Prognostic significance of sarcopenia and systemic inflammation for patients with renal cell carcinoma following nephrectomy.

Background: To clarify the prognostic effect of preoperative sarcopenia and systemic inflammation, and to develop a nomogram for predicting overall survival (OS) of patients with renal cell carcinoma (RCC) following partial or radical nephrectomy. Methods: Patients with RCC following nephrectomy from the First Affiliated Hospital of Soochow University during January 2018 to September 2020 were included in this study. The relationship between sarcopenia and inflammatory markers was identified by logistic regression analysis. Then univariable Cox regression analysis, LASSO regression analysis and multivariable Cox regression analysis were analyzed sequentially to select the independent prognostic factors. Kaplan-Meier survival curves were applied to ascertain the prognostic value. Finally, the identified independent predictors were incorporated in a nomogram, which was internally validated and compared with other methods. Results: A total of 276 patients were enrolled, and 96 (34.8%) were diagnosed with sarcopenia, which was significantly associated with neutrophil-to-lymphocyte ratio (NLR). Sarcopenia and elevated inflammation markers, i.e., NLR, platelet-to-lymphocyte ratio (PLR) and the modified Glasgow Prognostic Score (mGPS), were independent factors for determining the OS. The model had good discrimination with Concordance index of 0.907 (95% CI: 0.882-0.931), and the calibration plots performed well. Both net reclassification index (NRI) and integrated discriminant improvement (IDI) exhibited better performance of the nomogram compared with clinical stage-based, sarcopenia-based and integrated "NLR+PLR+mGPS" methods. Moreover, decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 20%. Conclusions: Preoperative sarcopenia was significantly associated with NLR. A novel nomogram with well validation was developed for risk stratification, prognosis tracking and personalized therapeutics of RCC patients.

Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro.

Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor-κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.

Early bone formation in mini-lateral window sinus floor elevation with simultaneous implant placement: An in vivo experimental study.

OBJECTIVE: To investigate the early bone formation in beagles with mini-lateral window sinus floor elevation and simultaneous implant placement. MATERIAL AND METHODS: Six beagles were selected for the split-mouth design procedures. In each animal, one maxillary recess received a 5 mm-diameter mini-round lateral osteotomy (test group), and the contralateral maxillary recess received a large rectangular osteotomy (10 mm long and 8 mm wide), (control group). Simultaneous implant installation was executed on bilateral maxillary recesses. Tetracycline and calcein dyes were administered on the 14th, 13th days and the 4th, 3rd days prior to sacrifice, respectively. After 8 weeks of healing, the beagles were euthanized for fluorescent labeling and histomorphometric analyses. RESULTS: In both groups, new bone formation initiated from the circumferential native bone of the maxillary recesses and extended toward the central sub-recess cavities. The maxillary recesses with the mini-window procedures exhibited superior mineral apposition rate, bone formation rate, and the percentage of new bone area to those of the group exposed to large osteotomy procedure (p < .05). While there was no significant difference in the value of bone-to-implant contact, the mini-window group displayed a tendency for an increase in this aspect (p > .05). Bone formation rate and new bone amount were not statistically correlated with bone-to-implant contact (p > .05). CONCLUSION: The hypothesis that mini-lateral window sinus floor elevation with simultaneous implant placement would improve early new bone formation in augmented sinus compared with large lateral window procedure is accepted.

Optimized beagle model for maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement.

OBJECTIVE: This study was performed to establish an optimized beagle model for maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement. METHODS: Twelve beagles underwent maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement through sites selected by analyzing preoperative cone beam computed tomography (CBCT) images. During the experiment, no maxillary teeth were extracted and the infraorbital nerve was not severed. The osteotomy was only 5 mm in diameter. The implant stability quotient was measured, and postoperative CBCT was used to detect the condition of the sinus membrane and bone augmentation. RESULTS: The site corresponding to the tip of the highest dental cusp of the maxillary fourth premolar was suitable for the procedure, and the implant site was on the palatal bone plate. All implants achieved good primary stability. Postoperative CBCT showed no sinus membrane perforation, and the implants penetrated into the sinus cavity surrounded by bone substitute. CONCLUSION: The herein-described optimized model with mini-lateral osteotomy and without extraction or severing of the infraorbital nerve was minimally invasive, retained more lateral bone of the sinus, and achieved good sinus floor-lifting results. This model is highly reproducible and merits wider application.

CBCT-based 3D MRA and angiographic image fusion and MRA image navigation for neuro interventions.

Digital subtracted angiography (DSA) remains the gold standard for diagnosis of cerebral vascular diseases and provides intraprocedural guidance. This practice involves extensive usage of x-ray and iodinated contrast medium, which can induce side effects. In this study, we examined the accuracy of 3-dimensional (3D) registration of magnetic resonance angiography (MRA) and DSA imaging for cerebral vessels, and tested the feasibility of using preprocedural MRA for real-time guidance during endovascular procedures.Twenty-three patients with suspected intracranial arterial lesions were enrolled. The contrast medium-enhanced 3D DSA of target vessels were acquired in 19 patients during endovascular procedures, and the images were registered with preprocedural MRA for fusion accuracy evaluation. Low-dose noncontrasted 3D angiography of the skull was performed in the other 4 patients, and registered with the MRA. The MRA was overlaid afterwards with 2D live fluoroscopy to guide endovascular procedures.The 3D registration of the MRA and angiography demonstrated a high accuracy for vessel lesion visualization in all 19 patients examined. Moreover, MRA of the intracranial vessels, registered to the noncontrasted 3D angiography in the 4 patients, provided real-time 3D roadmap to successfully guide the endovascular procedures. Radiation dose to patients and contrast medium usage were shown to be significantly reduced.Three-dimensional MRA and angiography fusion can accurately generate cerebral vasculature images to guide endovascular procedures. The use of the fusion technology could enhance clinical workflow while minimizing contrast medium usage and radiation dose, and hence lowering procedure risks and increasing treatment safety.