Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.

Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF-α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF-α treatment and miR-27a-3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF-α and decreased level of bone miR-27a-3p, and in vitro TNF-α treatment inhibited miR-27a-3p expression in BMSCs. In addition, miR-27a-3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red-S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled-related protein 1 (Sfrp1) as a downstream target of miR-27a-3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF-α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR-27a-3p on the osteogenic differentiation of BMSCs. Furthermore, the miR-27a-3p-Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a-ß-catenin signalling. In summary, this study revealed that TNF-α regulated a novel miR-27a-3p-Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

Sappanone A Alleviated IL-1ß-Induced Inflammation in OA Chondrocytes through Modulating the NF-κB and Nrf2/HO-1 Pathways.

Objective: This study was to examine the anti-inflammatory effect of sappanone A on interleukin- (IL-) 1ß-stimulated osteoarthritis (OA) chondrocytes. Methods: Chondrocytes were pretreated with sappanone A for 2 h before subsequent IL-1ß stimulation. The mRNA expression levels of iNOs, COX-2, aggrecan, and collagen-II were measured with qRT-PCR. The levels of TNF-α, IL-6, IL-8, MMP-3, and MMP-13 were determined by ELISA. The protein levels of iNOs, COX-2, ADAMTS-4, ADAMTS-5, aggrecan, collagen-II, p-p65, p65, IκBα, Nrf2, and HO-1 were assessed by Western blot. Results: Sappanone A inhibited the IL-1ß-stimulated production of NO, PGE2, iNOS, COX-2, TNF-α, IL-6, and IL-8 in OA chondrocytes. In addition, sappanone A suppressed the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1ß-stimulated OA chondrocytes. The degradation of ECM components was reversed by sappanone A. Sappanone A prevented NF-κB activation while enhanced Nrf2/HO-1 activation in IL-1ß-treated chondrocytes. Conclusion: Sappanone A may be a potent therapeutic agent for OA.

Undercorrection: the undesired effect of compression on the osteotomy gap of the medial opening wedge high tibial osteotomy and its clinical significance.

INTRODUCTION: Undercorrection is a common problem in opening wedge high tibial osteotomy (OWHTO). We investigated the compression effect of cortex screw on the osteotomy gap and its clinical significance. MATERIALS AND METHODS: A standard OWHTO using the TomoFix plate was conducted on 20 bone models in two groups to get a 10-mm medial osteotomy gap. A cortex screw was used temporarily in a neutral (at the center) and an eccentric position (near the inclined plane) of the dynamic hole in group 1 and group 2, respectively. The mean of undercorrection observed in the two groups was compared using an independent t test. Also, the effect of compression on the gap between the plate and medial tibial cortex, and the osteotomy gap was evaluated using a Sine rule. Besides, the mean undercorrection observed was assessed for clinical significance based on the effect on the weight-bearing axis (WBA) using a Cosine Rule. RESULTS: The mean undercorrection was 1.3 ± 0.6 mm and 2.6 ± 0.6 mm in group 1 and group 2, respectively. A significantly greater undercorrection was observed in group 2 (p < 0.001). The correction loss in group 2 has resulted from combinations of the sliding effect of the dynamic hole and oblique compression effect over the gap between the plate and medial tibial cortex whereas in group 1 it has only resulted from the oblique compression effect. The observed undercorrection in group 2 has resulted in clinically significant WBA shift (10%) over the width of the tibial plateau. CONCLUSIONS: In OWHTO, compression is important for the stability and healing of osteotomy, but it can also cause loss of correction. In patients requiring large correction, the surgeon should control the amount of compression required and consider making extra osteotomy gap to avoid undercorrection. Furthermore, the placement of cortex screws in neutral is essential to lower the risk of undercorrection.

Preoperative Planning Using 3D Printing Technology in Orthopedic Surgery.

The applications of 3D printing technology in health care, particularly orthopedics, continue to broaden as the technology becomes more advanced, accessible, and affordable worldwide. 3D printed models of computed tomography (CT) and magnetic resonance image (MRI) scans can reproduce a replica of anatomical parts that enable surgeons to get a detailed understanding of the underlying anatomy that he/she experiences intraoperatively. The 3D printed anatomic models are particularly useful for preoperative planning, simulation of complex orthopedic procedures, development of patient-specific instruments, and implants that can be used intraoperatively. This paper reviews the role of 3D printing technology in orthopedic surgery, specifically focusing on the role it plays in assisting surgeons to have a better preoperative evaluation and surgical planning.

[Expression Level and Clinical Significance of VEGF, IL-17, ß2-MG and IL-35 in Patients with Multiple Myeloma].

OBJECTIVE: To explore the expression and clinical significance of VEGF, IL-17, ß2-MG and IL-35 in patients with multiple myeloma. METHODS: A total of 83 patients with multiple myeloma (MM) from January 2012 to December 2016 were enrolled in MM group, 36 healthy subjects were enrolled in control group. The levels of IL-17, IL-35 and VEGF in serum were detected by ELISA. The levels of ß2-MG in serum were measured by radioimmunoassay. The differences of different indexes between 2 groups were compared. RESULTS: The serum levels of IL-17, VEGF and ß2-MG in serum of III stage were higher than that in II stage, which was higher than that in I stage and control group (P<0.05). The levels of IL-35 in the control group were significantly higher than those in the I,II,III stage group (P<0.05). The levels of IL-17, VEGF and ß2-MG in serum of progress period were higher than those in stable phase and control group, level of IL-35 in serum of control group was significantly higher than that in the stable phase and progress period group (P<0.05). The correlation analysis showed that the level of serum IL-17 positively correlated with VEGF, ß2-MG expression (r=0.65, 0.58, P<0.05); and the serum IL-17 levels were negatively correlated with IL-35 levels (r=-0.42, P<0.05). CONCLUSION: The anomalous levels of IL-17, IL-35, IVEGF and ß2-MG expressions correlate with the progression and prognosis of patients with multiple myeloma.

High expression of TRIM29 (ATDC) contributes to poor prognosis and tumor metastasis by inducing epithelial­mesenchymal transition in osteosarcoma.

The association of TRIM29 overexpression with cancer progression and poor clinical prognosis has been reported in the context of several types of cancers. In the present study, we investigated the prognostic relevance of TRIM29 and its involvement in the progression of human osteosarcoma. To the best of our knowledge, this is the first study to demonstrate a major role of TRIM29 in osteosarcoma. Our results showed that the expression of TRIM29 in osteosarcoma tissues was much higher than that in normal bone tissues. Furthermore, TRIM29 expression was significantly correlated with tumor size, recurrence, metastasis and overall survival time. High expression of TRIM29 and presence of metastasis were independent predictors of poor prognosis in these patients. Both protein and mRNA expression of TRIM29 in osteosarcoma cell lines were significantly higher than those in osteoblast cell line, hFOB1.19. Moreover, the results indicated that TRIM29 promoted migration and invasive growth of osteosarcoma cells by inducing epithelial-mesenchymal transition. Therefore, ectopic expression of TRIM29 potentially contributes to metastasis and poor prognosis in patients with osteosarcoma. In summary, TRIM29 is a potential prognostic biomarker and a therapeutic target for patients with osteosarcoma.