Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing.

A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin ß3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.

Effects of low-temperature degradation on the surface roughness of yttria-stabilized tetragonal zirconia polycrystal ceramics: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: A wide range of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) ceramics have been applied for dental restorations. However, whether hydrothermal aging affects the surface roughness of Y-TZP is unknown. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the effects of low-temperature degradation (LTD) on the surface roughness of Y-TZP ceramics. MATERIAL AND METHODS: This report follows the Preferred Reporting Items for Systematic Reviews and Qualitative Analyses statement. The literature search was conducted with Medline through the PubMed, Web of Science, and Cochrane Library with no publication year limits. The screening and quality assessment were performed by 2 independent reviewers. The studies comparing the surface roughness of Y-TZP ceramics after LTD by using steam autoclave aging were included in the meta-analysis. Meta-analyses were conducted with a random-effects model (α=.05) by using Review Manager Software (Cochrane Collaboration). RESULTS: Of the 203 potentially relevant studies, 32 full texts were assessed for eligibility. A total of 17 articles were included in the systematic review, and 15 were included in the qualitative analyses. The results showed no significant difference in the arithmetic average height (Ra) values between the nonaged and aged Y-TZP (P=.670; mean difference=0.01; 95% confidence interval=-0.03 to 0.05). Subgroup analyses revealed that the aging duration (P=.003) and specimen preparation (P=.010) contributed significantly to the changes in the surface roughness of the Y-TZP ceramics. CONCLUSIONS: Although LTD was found to have no significant effects on the surface roughness of Y-TZP ceramics, the effects of LTD depended on the duration of the steam autoclave process and the specimen preparation.

[Correlation between adenoid hypertrophy, maxillary sinus mucosal thickening and dentofacial development in children].

PURPOSE：To investigate the effects of adenoid hypertrophy and maxillary sinus mucosal thickening on dentofacial development. METHODS：The selected subjects were divided into 4 groups according to the inclusion criteria: group A (adenoid hypertrophy with maxillary sinus mucosal thickening), group B (adenoid hypertrophy without maxillary sinus mucosal thickening), group C (normal adenoid with maxillary sinus mucosal thickening), and group D (normal adenoid without maxillary sinus mucosal thickening). There were 20 subjects in each group, aging from 12 to 14 years old. The volume of maxillary sinus was measured by Mimics software. The adenoid, dental arch width, basal bone width and palatal height were measured by Dolphin software and dentofacial measurements were performed in the lateral cephalograms derived from cone-beam CT (CBCT). The data were analyzed with SPSS 24.0 software package. RESULTS： There was no significant difference in dentofacial measurements between group B and group D or group C and group D，except for ANB angle (P<0.05). Compared with group D, SNB, ANB, Wits appraisal, NA-APo, MP-HP, N-Me, S-Go/N-Me, N-ANS (perp HP), sum of three angles, Ar-Go of group A were significantly different (P<0.05). Neither left nor right maxillary sinus bony volume had significant difference between group B and D or group C and D. CONCLUSIONS： Both adenoid hypertrophy and maxillary sinus mucosal thickening have impact on dentofacial development. Moderate or more severe adenoid hypertrophy with maxillary sinus mucosal thickening has greater impact on dentofacial development over adenoid hypertrophy or maxillary sinus mucosal thickening alone.

Elevation of serum uric acid and incidence of type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: Recently, several cohort studies suggested a positive relationship between serum uric acid (SUA) and type 2 diabetes mellitus (T2DM), which is inconsistent with the results of functional research. Our aim was to further evaluate this correlation by conducting a systematic review. METHODS: Computerized literature searches of the Medline database, EMBASE database, and PubMed were used to evaluate the relationship between SUA and T2DM in cohort studies. Cochran's Q and I2 statistics were used to evaluate heterogeneity among studies, and pooled relative risk (RR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated using random-effects and fixed-effects models. The summary RR and OR of per 1 mg/ml-SUA increase were calculated separately because of their different epidemiological implications and calculation methods. Additionally, sensitivity analysis, stratified analysis, meta-regression, and multiple meta-regression were applied to investigate the heterogeneity among studies. RESULTS: A total of 970 articles were retrieved from the searches. Sixteen publications of cohort studies containing 61,714 participants were included. The pooled RR was 1.131 (95% CI: 1.084-1.179) with significant heterogeneity among studies (I2  = 51.9%, P = 0.018). Adjusted RR to evaluate the stability of the relationship between SUA and T2DM in the sensitivity analysis was similar (RR = 1.140, 95% CI: 1.087-1.197), with statistically significant heterogeneity (I2  = 54.5%, P = 0.015). Stratified analysis and meta-regression showed that the positive relationship remained irrespective of age, sex, region, and adjustment for confounding factors including body mass index, fasting blood glucose, systolic blood pressure, diastolic blood pressure, alcohol consumption, smoking, blood cholesterol, waist circumference, fatty liver, and drugs affecting SUA. CONCLUSION: Although SUA is independently associated with development of T2DM, insulin resistance increased as the baseline SUA concentration increased; thus, the correlation between SUA and T2DM requires further evaluation and the baseline insulin resistance status should also be considered.