COL3A1 is a potential diagnostic biomarker for synovial chondromatosis and affects the cell cycle and migration of chondrocytes.

BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.

LncRNA HOTAIR influences cell proliferation via miR-130b/PTEN/AKT axis in IDD.

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD.Abbreviations : IDD; intervertebral disc degeneration ncRNAs; non-coding RNAs lncRNAs; long non-coding RNAs miRNAs; microRNAs NP; nucleus pulposus qRT-PCR; quantitative reverse transcription-PCR LBP; Low back pain ORF; open reading frame HOTAIR; Hox transcript antisense intergenic RNA FAF1; Fas-associated protein factor-1 Erk; extracellular signal-regulated kinase TUG1; Taurine Up-regulated Gene 1 HIF1A hypoxia-inducible factor 1-alpha PI3K; phosphoinositide-3 kinase AIS; adolescent idiopathic scoliosis ECM; extracellular matrix LN;lupus nephritis CT;computed tomography MRI; magnetic resonance imaging PBS; phosphate-buffered salin PBS; phosphate-buffered salin PVDF; polyvinylidene fluoride TBST; Tris-buffered saline Tween ECL; enhanced chemiluminescence RIP; RNA immunoprecipitation.

lncRNA LSINCT5 Regulates miR-20a-5p/XIAP to Inhibit the Growth and Metastasis of Osteosarcoma Cells.

BACKGROUND: More and more evidence has shown that non-coding RNA (ncRNA), including long ncRNA (lncRNA) and micro RNA (miRNA), plays a crucial regulatory role in osteosarcoma (OS). Previously, we revealed a Rho-related coiled coil incorporating protein kinase 1(XIAP). A transfer-related gene is negatively regulated by microRNA-20a-5p (miR-20a-5p) and plays the role of oncogene in OS. It is not clear if any lncRNA is involved in the axial upstream of miR-20a-5p/XIAP. METHODS: Expression of LSINCT5 and miR-20a-5p/XIAP in OS tissues was determined through qRT-PCR (qP). The proliferation and migration/invasion activity of OS cells were tested through CCK-8/and transwell assay, respectively. The changes on expression of XIAP were examined through qRT-PCR and Western blot (WB). Targeted binding between LSINCT5, miR-20a-5p, and XIAP has been verified using dual luciferase reporter gene analysis, RNA Immunoprecipitation (RIP), and RNA pull-down experiments. The effect of LSINCT5 on tumor growth was determined by tumor allograft test. RESULTS: In this study, elevated LSINCT5 was found in OS tissue samples and OS cell strains, and the increased LSINCT5 was strongly related to the adverse prognosis of clinical patients. Functional assays showed that inhibition of LSINCT5 could up-regulate miR-20a-5p-mediated OS cells proliferation and metastasis. WB analysis and qP analysis showed that LSINCT5 regulated XIAP by mediating miR-20a-5p. Further cell behavior experiments showed that LSINCT5 acted as a miR-20a-5p sponge to inhibit proliferation and metastasis caused by XIAP. Finally, the results of animal models in vivo showed that LSINCT5 could regulate the tumor growth of OS. CONCLUSION: LncRNA LSINCT5 acts as an oncogene and promotes XIAP mediated growth and metastasis as competitive endogenous RNA (ceRNA) in OS.

Analysis of the clinical efficacy of tumor resection methods used in 20 patients with clavicular tumor.

BACKGROUND: To retrospectively analyze the tumor resection method used in 20 patients with clavicular tumors and evaluate its clinical efficacy. METHODS: A total of 9 patients with clavicular benign tumors underwent intracapsular resection, and 11 patients with clavicular malignant tumors underwent tumor resection from May 2012 to May 2017. Of the 11 patients, 5 underwent clavicular reconstruction using the plate-cement complex. Surgical efficacy was assessed using the Musculoskeletal Tumor Society, Constant-Murley, and American Shoulder and Elbow Surgeons shoulder outcome scores preoperatively until 12 months postoperatively. RESULTS: The average duration of follow-up care was 33.7 (12-71) months. Of the 20 patients, 3 patients died, 3 survived with tumor recurrence or metastasis, and 14 survived with no tumor recurrence. Among the 5 patients who underwent resection of malignant clavicular tumors and reconstruction, 2 underwent a re-operation because of a loose screw and plate displacement. In the functional assessment of the shoulder joint, patients with benign and malignant clavicular tumors showed significantly higher scores postoperatively compared with preoperative scores. For malignant clavicular tumors, no significant improvement was observed when comparing the non-reconstruction and reconstruction groups. CONCLUSIONS: Surgery is an optimal treatment for clavicular tumors. In patients with benign clavicular tumors, simple intracapsular resection can achieve a satisfactory prognosis. Reconstruction of a clavicular defect after resection of a clavicular malignant tumor is not recommended.

Vaccarin prevents titanium particle-induced osteolysis and inhibits RANKL-induced osteoclastogenesis by blocking NF-κB and MAPK signaling pathways.

Wearing titanium particle-induced osteoclastogenesis, accompanied by peri-implant osteolysis, is the main cause of long-term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri-implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti-inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle-induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL-induced osteoclastogenesis, fusion of F-actin rings, bone resorption, and expression of osteoclast marker genes in a dose-dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL-induced osteoclastogenesis via the inhibition of NF-κB and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c-Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle-induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri-implant osteolysis.

OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration.

The present study aimed to investigate the associations between three distinct osteoprotegerin (OPG) gene polymorphisms and the risk of intervertebral disc degeneration (IDD). A total of 200 IDD patients and 200 healthy controls were recruited from the Department of Spine Surgery at the First Affiliated Hospital of the University of South China (Hengyang, China) between January 2013 and May 2014. The allele, genotype and haplotype frequency distributions of three OPG polymorphisms in the study and control populations were analyzed by polymerase chain reaction prior to restriction fragment length polymorphism or high resolution melting assays. In addition, serum OPG levels were measured via an ELISA. The genotype and allele frequencies of the OPG rs2073617 polymorphisms were significantly higher in the IDD patients, as compared with the control group (P<0.05). Furthermore, carriers of the C allele exhibited a higher risk of IDD, as compared with carriers of the T allele (P<0.001). Conversely, the genotype and allele frequencies of the two other gene polymorphisms, rs2073618 and rs3102735, showed no significant differences between the patients and controls (P>0.05). The serum OPG levels were significantly higher in IDD patients with TT, TC and CC genotypes at the OPG rs2073617 polymorphism, as compared with the control group (P<0.05). Logistic-regression analysis suggested that high serum levels of OPG were positively correlated with IDD risk, whereas the T-C-A, T-G-A and T-G-G haplotypes were negatively correlated with IDD risk (P<0.05). Furthermore, the G-T-G haplotype was associated with protection against IDD (P=0.008), whereas the G-C-G haplotype was associated with an elevated susceptibility to IDD (P=0.007). The results of the present study suggested that OPG rs2073617 polymorphisms and upregulated serum levels of OPG were associated with an increased risk of IDD, whereas the T-C-A, T-G-A and T-G-G haplotypes were protective factors for IDD. The results of the present study suggested that the OPG gene polymorphism may have an important role in the progression of IDD, and its serum level may function as a valuable predictive indicator of the severity of degenerative disc diseases.

Anterior transsternal approach for treatment of upper thoracic vertebral tuberculosis.

OBJECTIVE: To study an anterior transsternal approach for treatment of upper thoracic vertebral (T(l)-T(4)) tuberculosis (TB). METHODS: Sixteen patients with upper thoracic vertebral TB underwent anterior decompression and fusion through an anterior transsternal approach. There were nine men and seven women with a mean age of 48.6 ± 2.3 years (range, 37 to 72 years). The involved area included T(l) in three patients, T(2) in one, T(2) and T(3) in four, T(3) in two, T(3) and T(4) in four, and T(4) in two. The "inside window of the brachiocephalic artery" was used to access T(1) and T(2) lesions, and the "outside window of the brachiocephalic artery" for T(3) and T(4) lesions, for T2 and T3, both "windows" were used. According to the Frankel grading system, two patients were of Grade A, one Grade B, two Grade C, six Grade D and five Grade E. The kyphosis Cobb's angle ranged from 15°-40° (mean, 22° ± 2.5°) preoperatively. RESULTS: All patients tolerated surgery wel1. The operation time was 120-150 minutes and bleeding during operation 300-600 ml. The kyphosis Cobb's angle ranged from 10°-25° (mean, 17° ± 2.5°) postoperatively. Eight patients with preoperative neurologic deficit had improved. During the follow-up period, all cases healed without any recurrence. There was no failure of internal fixation. Spinal bone fusion occurred after 3-6 months (mean, 4.2 months) after bone graft in all patients. CONCLUSION: The anterior transsternal approach provides safe and effective access for surgical treatment of upper thoracic TB.

C2 pedicle screw and plate combined with C1 titanium cable fixation for the treatment of atlantoaxial instability not suitable for placement of C1 screw.

STUDY DESIGN: A method of atlantoaxial stabilization using individual fixation of the C1 posterior arch and the C2 pedicle with C2 pedicle screws and plates combined with C1 titanium cables is described. In addition, the clinical results of this method on 8 patients are described. OBJECTIVE: To describe the method and the clinical and radiographic results for posterior C1-C2 fixation with a combined implant system. SUMMARY OF BACKGROUND DATA: Stabilization of the atlantoaxial complex is a challenging procedure because of the unique anatomy of this region. Fixation by plate or rod and C1 and C2 screw and structural bone grafting leads to excellent fusion rates. The technique is technically demanding and has a potential risk of the injuries to the vertebral artery, the internal carotid artery, spinal cord, and hypoglossal nerves. In addition, how to stabilize the atlantoaxial complex in the cases not suitable for placement of C1 screw is not described in the literature. To address these limitations, a method of C1-C2 fixation has been developed: bilateral insertion of C2 pedicle screws and rolling of C1 titanium cable through the posterior arch of atlas and the cranial hole of the plate, followed by C1-C2 plate fixation. METHODS: From February 2003 to March 2006, 8 patients with atlantoaxial instability and not suitable for placement of C1 screw were included in this study: 5 cases of broken C1 pedicle screw trajectory and 3 cases of C1 anatomic anomalies. Skull traction was performed in each patient preoperatively. The pedicle screws were inserted into C2 pedicles in the direction as its axis. C1 titanium cable was rolled superior to lower through posterior arch of atlas in the cases not suitable for placement of C1 screw. The C1-C2 plate was slightly bent to fit the upper cervical contour. Hyperflexion alignment of the atlantoaxial complex was corrected by application of extension force created by tightening of the nut on the pedicle screws and the C1 titanium cable, which was passed through the cranial hole of the plate. Morselized autogenous cancellous iliac grafts were placed on the surface of the posterior arches of both atlas and axis. All patients were assessed clinically for neurologic recovery by Odom's method. RESULTS: There were 5 males and 3 females with a mean age of 37.8 years (range, 17 to 59 y). There were 2 cases of old odontoid fracture, 2 cases fresh odontoid fracture (Aderson II C), 2 cases atlas transverse ligament laxation, 2 cases atlas transverse ligament rupture, and in these cases, 5 cases had failed placement of C1 screw because of broken C1 pedicle screw trajectory and 3 cases not suitable for placement of C1 screw because of anatomic anomalies. There were no spinal cord and vertebral artery and nerve injury after surgery. Follow-up duration was from 18 to 55 months with the average of 29 months. The plant bones all fused and there were no internal fixation rupture and mobility. All the patients showed improvement. CONCLUSIONS: C2 pedicle screw and plate combined with C1 titanium cable could be used to treat atlantoaxial instability in the cases not suitable for placement of C1 screw.

Treatment of osteonecrosis of femoral head with BMSCs-seeded bio-derived bone materials combined with rhBMP-2 in rabbits.

OBJECTIVE: To evaluate the effect of autologous bone marrow mesenchymal stem cells (BMSCs) seeded bio-derived bone materials (BBM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in repairing defect of osteonecrosis of femoral head (ONFH). METHODS: Early-stage osteonecrosis in the left hip was induced in 36 adult New Zealand white rabbits (provided by the Animal Center of Guangxi Medical University, Nanning, China) after core decompression and delivery of liquid nitrogen into the femoral head. Then the animals were divided into three groups according to the type of implants for bone repair: 12 rabbits with nothing (Group I, the blank control group), 12 with BBM combined with rhBMP-2 (Group II), and 12 with BMSCs-seeded BBM combined with rhBMP-2 (Group III). At 4, 8, and 12 weeks after surgery, X-ray of the femoral head of every 4 rabbits in each group was taken, and then they were killed and the femoral heads were collected at each time point, respectively. Gross observation was made on the femoral heads. After hematoxylin and eosin staining, Lane-sandhu scores of X-ray and bone densitometry were calculated and the histomorphometric measurements were made for the new bone trabeculae. RESULTS: At 12 weeks after surgery, two femoral heads collapsed in Group I, but none in Group II or Group III. X-ray examination showed that the femoral heads in Group I had defect shadow or collapsed while those in Group II had a low density and those in Group III presented with a normal density. Histologically, the defects of femoral heads were primarily filled with no new bone but fibrous tissues in Group I. In contrast, new bone regeneration and fibrous tissues occurred in Group II and only new bone regeneration occurrd in Group III. Lane-sandhu scores of X-ray, bone mineral density and rate of new bone in trabecular area in Group III were higher significantly than those of the other two groups. CONCLUSIONS: Our findings indicate a superior choice of repairing the experimental defect of ONFH with BMSCs- seeded BBM combined with rhBMP-2.

Surgical management for upper thoracic spine tumors by a transmanubrium approach and a new space.

The anterior aspect of the upper thoracic spine is a difficult region to approach in spinal surgery. Many vital structures including osseus, articular, vascular and nervous ones hinder the exposure. With increasing frequency, spine surgeons are being asked to provide decompression and stabilization in patients with spinal tumors. The traditional exposure is between the esophagus and trachea medially and the left common carotid or the brachiocephalic artery (BCA) laterally, and the disadvantages were that the ligation and section of the left innominate vein is proposed to reach T4 and the injury of the thoracic duct could occur. The right space of the BCA or the ascending aorta (AA) (the exposure between the right brachiocephalic vein and the BCA or between the AA and superior caval vein) is recommended in exposing the upper thoracic vertebrae; this new space is technically feasible; the exposure is sufficient for vertebral body resection and reconstruction and fixation. Twenty-eight patients with upper thoracic spine tumors underwent surgery by the use of this new space between June 2000 and October 2005. A strut graft was fixed anteriorly after decompression of the spinal cord. Levels C7-T5 can be well exposed through this new space, allowing complete vertebral body removal at level T1-T4. After body removal, the posterior longitudinal ligament is well exposed, allowing complete release of the spinal cord. Curettage was performed in one case of aneurysmal bone cyst and three cases of bone giant cell tumors. For other tumors, vertebrectomies or sagittal resections were performed. Four patients underwent surgery by a combination of anterior and posterior approach.

[Precision-fit surface hemiarthroplasty of the hip for the treatment of the femoral head osteonecrosis].

OBJECTIVE: To evaluate the outcome of precision-fit surface hemiarthroplasty in the treatment of femoral head osteonecrosis. METHODS: The clinical data of 41 patients (48 hip joints) with femoral head osteonecrosis were reviewed. Of them, 30 were male and 11 were female, average age was 37 years old (ranging from 29 - 49). Thirty-five patients were at Ficat stage III and 13 at Ficat stage IV, their acetabula were relatively normal. The 41 patients (48 hip joints) underwent precision-fit surface hemiarthroplasties. RESULTS: The mean duration of follow-up was 5.2 years. The average UCLA hip score at follow-up was improved significantly from 3.1 to 9.1 points for pain, 4.4 to 9.2 points for walking, and 5.5 to 7.1 points for activity (P = 0.001). The satisfaction rate was 88.6% for 35 at Ficat stage III, 69.2% for 13 at stage IV (P = 0.25). Eight hips failed; the UCLA hip score was not improved significantly; the postoperative X-ray examination showed that 7 femoral prostheses were implanted in a varus orientation (the angle between the femoral prosthesis stem and the anatomic axis of the femoral shaft was lower than angle of 130 degrees). Five-year survival rate was 83.0%. CONCLUSIONS: Precision-fit surface hemiarthroplasty of the hip has the satisfactory result in treatment of the femoral head osteonecrosis on the basis of observing strictly operative indications and improving operative technique.