Up-regulation of urinary exosomal hsa-microRNA-200b-3p and hsa-microRNA-206 in patients of steroid-induced osteonecrosis of femoral head.

The aim of this study was to determine the value of microRNAs (miRNAs) in urinary exosomes in the diagnosis of steroid-induced osteonecrosis of femoral head (SONFH). RNA was extracted from urinary exosomes from 9 SONFH patients and 9 hip osteoarthritis (HOA) patients with age and gender matched and then miRNAs were analyzed by next generation sequencing. Intriguingly, 15 miRNAs including hsa-miR-200b-3p and hsa-miR-206 were significantly upregulated in exosomes from SONFH patients. Furthermore, qRT-PCR and area under curve (AUC) analysis of an independent cohort of 30 SONFH patients, 10 HOA patients and 10 healthy donors confirmed that hsa-miR-200b-3p and hsa-miR-206 were upregulated in SONFH samples which AUC values were 0.938 (95% CI: 0.828-1) and 0.926 (95% CI: 0.806-1) respectively. GO function, KEGG pathway, miRNAs-mRNAs network and protein-protein interaction (PPI) network were also constructed to analyze potentially pathological mechanisms. The enriched functions and pathways included Hippo, PI3K-Akt, TGF-ß and Wnt signaling pathways. The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes might serve as non-invasive biomarkers for SONFH.

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species.

Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways in vitro, and prohibit bone loss induced by OVX in vivo. Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.

Mesenchymal Stem Cells-Derived Exosomes: A Possible Therapeutic Strategy for Osteoporosis.

Osteoporosis is a common age-related disorder characterized by low bone mass and deterioration in bone microarchitecture, leading to increased skeletal fragility and fracture risk. The pathophysiology of osteoporosis is multifactorial. It is related to the imbalance between osteoblasts and osteoclasts; reduced bone mass and increased adipogenesis in the bone marrow. Moreover, angiogenesis, inflammatory process and miRNAs have shown effects in the formation of osteoporosis. In the recent years, mesenchymal stem cells (MSCs) have been regarded as an excellent choice for cell-based tissue engineering therapy of osteoporosis. Growing evidence showed that paracrine effect has been considered as the predominant mechanism for the role of MSCs in tissue repair. Recently, many studies have proposed that MSCs-derived exosomes are effective for a variety of diseases like cancer, cardiovascular diseases, etc. However, whether the MSCs-derived exosomes could serve as a novel therapeutic tool for osteoporosis has not clearly described. In this review, we summarize the MSCs-derived exosomes and the relationship with osteogenesis, osteoclast differentiation, angiogenesis, immune processes and miRNAs. Finally, we suggest that MSCs-derived exosomes might be a promising therapeutic method for osteoporosis in the future.

Hidden Blood Loss in Posterior Lumbar Fusion Surgery: An Analysis of Risk Factors.

STUDY DESIGN: Descriptive study. OBJECTIVES: This study aimed to evaluate the hidden blood loss (HBL) of patients who underwent lumbar fusion surgery for degenerative spine and to analyze its risk factors. SUMMARY OF BACKGROUND DATA: When planning transfusion strategies, blood loss calculation is important. However, in clinical practice, spine surgeons usually ignore the possibility that a large amount of HBL may occur after lumbar fusion surgery. MATERIALS AND METHODS: We studied the patients who underwent posterior lumbar fusion (PLF) surgery for degenerative spine from 2014 to 2015 in one institution. The patient's demographics, comorbid conditions, coagulation panel value, surgical time, number of levels fused, American Society of Anesthesiologists (ASA) classification, cell saver, preoperative hematocrit level, preoperative hemoglobin level, and postoperative complications were collected retrospectively. Pearson correlation analyses were used to find an association between patient characteristics and HBL. Multivariate linear analysis was used to determine independent risk factors of HBL. RESULTS: We reviewed 169 consecutive patients who underwent PLF surgery for degenerative spine in one institution. The mean amount of HBL was 588 mL, which was 39% of the total blood loss. On the basis of the model of multiple linear regression analysis, the multilevel fusion (P=0.001), surgical time (P=0.034), and fibrinogen level (P=0.027) were independent risk factors that contributed to HBL, but age of 60 years or above (P=0.110), postoperative complications (P=0.278), and cell saver were not (P=0.739). CONCLUSIONS: We conclude that a large amount of HBL may occur in patients who underwent PLF surgery for degenerative spine. In addition, significant hidden loss may have a correlation with postoperative mortality. Multilevel fused, surgical time, and fibrinogen level should be paid close attention when considering strategies of fluid infusion and blood transfusion.

Hidden Blood Loss in Anterior Cervical Fusion Surgery: An Analysis of Risk Factors.

STUDY DESIGN: A retrospective study. OBJECTIVES: Anterior cervical fusion surgery is widely used procedure in cervical spondylosis. When considering the blood reinfusion strategies of cervical fusion surgery, the amount of blood loss is one of the key elements. We usually calculate the blood loss according to the surgical bleeding plus the postoperative drainage; however, this method ignores the possibility that there may be hidden blood loss (HBL). METHODS: We performed a retrospective study to determine the risk factors for HBL in patients who underwent anterior cervical fusion surgery for degenerative spine from 2013 to 2016. The Pearson correlation, Spearman correlation, and multivariate liner analysis were used to find association between patient characteristics and HBL. RESULTS: A total of 107 consecutive patients who underwent anterior cervical fusion surgery for degenerative spine in our hospital were reviewed. The amount of HBL was 261 mL, or 50% of the total blood loss. According to the model of multiple linear regression analysis, patient sex (P = 0.028) and American Society of Anesthesiologists physical status classification (P = 0.029) were independent risk factors contributing to HBL, but preoperative hematocrit was not (P = 0.741). CONCLUSIONS: We concluded that sex and American Society of Anesthesiologists physical status classification were independent risk factors of HBL in anterior cervical fusion surgery. In addition, there was a high proportion of HBL in anterior cervical fusion. When considering the strategies of transfusion, we should pay attention to the risk factors for HBL.

PPAR-γ and Wnt Regulate the Differentiation of MSCs into Adipocytes and Osteoblasts Respectively.

BACKGROUND: Under the transcriptional control of numerous factors and intracellular signals, mesenchymal stem cells (MSCs) can differentiate into various cell types, including adipocytes and osteoblasts. However, the precise cellular signaling factors that determine the cell fate of MSCs in bone marrow remain largely unknown. OBJECTIVE: In this review, we focus on the ties of PPAR-γ and Wnt signaling in MSC differentiation into adipocytes and osteoblasts. RESULTS: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is well established as a prime inducer of adipogenesis, while the Wnt pathway is regarded as the master moderator of osteogenesis. A theoretical inverse relationship exists between adipogenic and osteogenic lineage commitment and differentiation: the differentiation toward an osteoblast phenotype occurs at the expense of an adipocyte phenotype. CONCLUSION: It has been proposed that the balance between osteogenic and adipogeneic MSC differentiation is disrupted in diverse areas of human health. Therefore, understanding the ties between PPAR- γand Wnt signaling in MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.