Dietary intervention reprograms bone marrow cellular signaling in obese mice.

Objectives: The current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity. Methods: Mice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt). Results: Weight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-ß-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group. Conclusions: Our findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual.

Comparative proteomic analysis identifies differentially expressed proteins and reveals potential mechanisms of traumatic heterotopic ossification progression.

Background: Traumatic Heterotopic Ossification (tHO) is one of complications of elbow fractures to the detriment of patients' rehabilitation, and the severity of tHO corresponds to the size of ectopic bone. It has yet to be elucidated which proteins and pathways underlying the progression of tHO, and biomarkers to predict the severity of tHO at early stage of the disease also need further investigation. Methods: In this study, a new rat model with distinct volume of ectopic bone was established first. Then a data-independent acquisition proteomics approach was used to investigate injured site tissues sequentially obtained from these rats (2, 7, 14, and 28 days post-injury). Differentially expressed analysis, functional annotation and co-expression analysis and protein-protein interaction network were performed to explore the pathways and hub proteins in the tHO progression. Clinical samples from a nest case-control study were used to validate the selected proteins for predicting the severity of tHO. Results: The Achilles Tenotomy (AT) induced significantly larger sizes of ectopic bone compared to Partial Achilles Tenotomy (PAT) in rat models. A total of 3547 quantifiable proteins were screened for differential expression analysis among the AT, PAT and control groups. The hierarchical clustering and expression pattern analysis revealed more apparent difference in the pathways such as oxidative phosphorylation, mitochondrial function, and sirtuin signaling between AT and PAT group at the early stage (2 dpi) of tHO. The co-expression analysis identified five hub proteins, UBA1, EIF3E, RPL17, RPL27, and RPS28. qPCR assay, immunoblot assay and immunohistochemistry assay verified that these proteins had higher expression level in the tissue samples of clinically relevant HO patients and clinically irrelevant HO patients than HO negative patients. Conclusion: The new established animal model and proteome profile could serve as a solid foundation for the comprehensive investigation of the progression of traumatic heterotopic ossification. And the identified 5 proteins (UBA1, EIF3E, RPL17, RPL27, and RPS28) may serve as potential biomarkers to predict the severity of tHO. The translational potential of this article: The proteins identified in this study may be the potential biomarkers and therapeutic targets for predicting and treating the tHO at early stage.

D-dimer for diagnosis of periprosthetic joint infection: A meta-analysis.

BACKGROUND: The D-dimer test is easily available to detect periprosthetic joint infection (PJI). This study aimed to estimate the diagnostic accuracy of the D-dimer test in PJI diagnosis and identify possible independent factors affecting the diagnostic value of this test. METHODS: MEDLINE and EMBASE databases identified literature until February 2020 that utilized the D-dimer test for PJI diagnosis. The pooled sensitivity, specificity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated to evaluate the diagnostic accuracy of the D-dimer test. Meta-regression and subgroup analyses were performed to assess potential heterogeneity. RESULTS: The databases identified 243 records, and eight studies were included in the final analysis. The pooled sensitivity and specificity of the D-dimer test for PJI diagnosis were 0.78 (95% confidence interval [CI], 0.69-0.84) and 0.74 (95% CI, 0.85-0.99), respectively. The AUCs and DORs of the D-dimer test were 0.83 (95% CI, 0.79-0.86) and 10 (95% CI, 4-24), respectively. The PLR and NLR of the D-dimer test for PJI detection were 3.0 (95% CI, 1.9-4.8) and 0.30 (95% CI, 0.20-0.47), respectively. The results of the meta-regression and subgroup analyses indicated that studies that excluded patients with hypercoagulation disorder had higher sensitivity (0.85 vs 0.86) and specificity (0.83 vs 0.62). The sensitivity of the D-dimer test also improved in studies that excluded patients with inflammatory arthritis (0.81 vs 0.75). CONCLUSION: The D-dimer test is a practical method for PJI diagnosis, especially in patients without history of hypercoagulation disorder and inflammatory arthritis.