Small non-coding RNAome changes during human chondrocyte senescence as potential epigenetic targets in age-related osteoarthritis.

Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.

[Bridging system for severe comminuted femoral fracture].

OBJECTIVE: To explore the clinical effect of bridging system in the treatment of severe comminuted femoral fracture. METHODS: From March 2016 to October 2018, 50 patients with severe comminuted femoral fracture including 35 males and 15 females, aged 48 to 72(54.6±8.7) years, were admitted. All cases were comminuted fractures of the femoral shaft, 16 with proximal femur fractures and 7 with distal femur fractures. All cases were all unilateral fractures, 23 on the left and 27 on the right. The time from injury to operation was 5 to 60 (26.7±13.3) hours. The cause of injury was traffic accident, 12 cases with high fall, 35 cases fell and 3 cases fell accidentally. The patients were treated with bridge combined internal fixation system, and the operative effect and fracture healing were analyzed. RESULTS: The operation was successful in all patients. There was no change to other fixed operation. The operation time was (75.8±12.3) min, the amount of bleeding was(356.4±64.8) ml, and there was no serious postoperative complications such as infection, internal fixation displacement, re fracture and nonunion. After 6 to 36 months follow-up, the fracture healing was evaluated by Warden's score. With the extension of observation time, Warden's score gradually increased, and the time of bone healing was(5.5±0.9) months. Harris score and HSS score were used to evaluate the function of hip and knee joint respectively. With the extension of time, Harris score and HSS score increased gradually. Six months after operation, Harris score was 83.5±11.2, HSS score was 79.7±10.5. During the follow-up period, there were no serious complications such as internal fixation displacement, re-fracture, nonunion of fracture and deep vein thrombosis of lower extremity. CONCLUSION: The bridge combined internalfixation system has better safety and effectiveness in the treatment of severe comminuted femoral fracture. As long as the requirements of local anatomy and biomechanics are strictly mastered and the operation risks are fully evaluated in combination with imaging, the better fixation effect can be achieved. The operation has less trauma, fewer complications and simple operation, which is believed to have a wider application potential. Due to the limited sample size and follow-up time, no clinical control was set up, the results of the study still need to be further verified by prospective trials.

Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway.

Galectin-1 (GAL1), a widely expressed ß­galacto-side-binding protein, exerts pleiotropic biological functions. GAL1 has been found to be upregulated in many malignancies; yet the role of GAL1 in the pathophysiology of human osteosarcoma (OS) remains uncertain. The present study was carried out to investigate the expression of GAL1 in human OS tissues and to explore its effects on the growth and invasion of OS cells. OS and corresponding adjacent non-cancerous tissues (ANCT) were collected from 30 consecutive cases. The expression of GAL1 was detected by immunohistochemical assay through tissue microarray procedure. Using small hairpin RNA (shRNA)-mediated GAL1 knockdown (Lv-shGAL1) in OS (MG-63 and U-2 OS) cells, we observed the changes in the malignant phenotype in OS cells in vitro and in vivo. As a consequence, the positive expression of GAL1 was significantly higher in OS tissues than that in the ANCT (63.3 vs. 36.7%, P=0.029), and was positively correlated with distant metastasis in the OS patients (P=0.022). Knockdown of GAL1 suppressed cell proliferative activities and invasive potential and induced apoptosis in OS cells with decreased expression of p38MAPK, p-ERK, Ki-67 and matrix metallopeptidase-9 (MMP-9) and increased expression of caspase-3. In addition, the tumor volume in the MG-63 subcutaneous tumor models treated with Lv-shGAL1 was significantly smaller than that in the negative control (NC) group (P<0.01). Altogether, our findings indicate that high expression of GAL1 is associated with distant metastasis of OS patients, and knockdown of GAL1 inhibits growth and invasion of OS cells possibly through inhibition of the MAPK/ERK pathway, suggesting that GAL1 may represent a potential target for the treatment of cancer.

Activation of receptor for advanced glycation end products contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated rats.

OBJECTIVE: The aim of present study was to test the hypothesis that activation of receptor for advanced glycation end products (RAGE) pathway contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated (SAD) rats. METHODS AND RESULTS: Experiment 1: 8 weeks after sinoaortic denervation, aortas were removed for measurement of AGE/RAGE pathway. Sinoaortic denervation in rats resulted in enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE in aortas. Experiment 2: 5 weeks after sinoaortic denervation, the rats received intraperitoneal injections of 500 µg soluble RAGE (sRAGE) daily for 3 weeks. Treatment of SAD rats with sRAGE attenuated aortic remodeling, marked by reduction in AW/length, wall thickness, proliferation of SMC, and collagen deposition, and improvement of endothelial function. Treatment of SAD rats with sRAGE abated aortic oxidative stress, marked by reduction in formation of malondialdehyde, reactive oxygen species, superoxide, peroxynitrite and 3-nitrotyrosine, and enhancement of ratio of GSH/GSSG. Treatment of SAD rats with sRAGE attenuated aortic mitochondrial dysfunction. Treatment of SAD rats with sRAGE suppressed aortic NFκB nuclear translocation and inflammation. Treatment of SAD rats with sRAGE restored aortic NO formation through upregulating eNOS and dimethylarginine dimethylaminohydrolase-2 and downregulating protein arginine methyltransferase-1. CONCLUSION: Activated RAGE contributed to aortic remodeling and endothelial dysfunction in SAD rats, possibly via induction of oxidative stress and inflammation, impairment of mitochondrial function, and reduction in NO bioavailability.

[Radiographic comparison of anterior cervical fusion after two-level discectomy or single-level corpectomy for two-level cervical spondylotic myelopathy].

OBJECTIVE: To compare the pre- and post-operative radiographic data of a single-level anterior cervical corpectomy and fusion (ACCF)or a two-level anterior cervical discectomy and fusion (ACDF) for patients with two-level cervical spondylotic myelopathy. METHODS: We retrospectively reviewed the lateral cervical radiographs of 110 patients undergoing a single-level ACCF or a two-level ACDF for the treatment of cervical myelopathy from March 2005 to May 2008. All of them underwent anterior cervical fusion using poly ether ether ketone (PEEK) cage or titanium meshes packed with autogenous bone and fixed-screw titanium plate fixation. A single-level ACCF (group of ACCF, n = 48) or a two-level ACDF (group of ACDF, n = 62) was performed. The following parameters were analyzed: cervical sagittal alignment, Cobb angles of fusion segments, graft collapse, adjacent-segmental degeneration and rate of bone fusion. RESULTS: During a follow-up period of 24 - 60 months, no significant differences existed in sagittal alignment, adjacent-segmental degeneration and rate of bone fusion between two groups. Graft subsidence and loss of Cobb angles of fusion occurred significantly more during the first 2 months post-operation than after 2 months in each group (P < 0.01). However, the group of ACCF subsided and lost more than the group of ACDF (P < 0.05). Caudal endplate subsidence significantly progressed after the first 2 months in the Group of ACCF (P < 0.05). CONCLUSION: Graft subsidence and loss of fusion segmental lordosis of two groups occur mainly in an early post-operation stage (first 2 months). The group of ACDF with PEEK cage is superior to the group of ACCF with titanium meshes in maintaining the height and lordosis of fusion segments. Single-level ACCF with titanium meshes continues subsiding at the caudal endplate of fusion segments even after 2 months.

Medial malleolus and deltoid ligament reconstruction in open ankle fractures with combination of vascularized fibular head osteo-tendinous flap and free flap transfers.

Treatment of the traumatic bone and soft tissue defect of the medial ankle is a challenge in reconstructive orthopedic surgery. In this report, we described a novel reconstruction procedure for the medial malleolus reconstruction using microsurgical transfer of the fibular head osteo-tendinous flap combined with a free latissimus dorsi flap (free LD flap) or a free anterolateral thigh flap (free ALT flap) in six patients. The sizes of the wounds ranged from 10 x 8 cm to 24 x 10 cm, and the sizes of the LD and ALT flaps were from 12 x 9 cm to 24 x 12 cm. All transplants survived. Five patients had primary wound healing. One patient had fibular graft and soft tissue infection that caused delayed healing. On average 4 months after surgery, all patients were able to stand and walk without crutch assistance. With a mean follow-up of 3.5 years (range, 1-5 years), all patients achieved stable ankles and were satisfied with the range of motion with excellent American Orthopedic Foot and Ankle Society functional scores (> 85). The fibular head resembles the medial malleolus in morphology. Vascularized fibular head transfer combined with a free flap provides satisfactory results for complex medial malleolus reconstruction.