PiRNA hsa_piR_019949 promotes chondrocyte anabolic metabolism by inhibiting the expression of lncRNA NEAT1.

BACKGROUND: Osteoarthritis is a prevalent degenerative joint condition typically found in individuals who are aged 50 years or older. In this study, the focus is on PIWI-interacting RNA (piRNA), which belongs to a category of small non-coding RNAs. These piRNAs play a role in the regulation of gene expression and the preservation of genomic stability. The main objective of this research is to examine the expression of a specific piRNA called hsa_piR_019949 in individuals with osteoarthritis, to understand its impact on chondrocyte metabolism within this condition. METHODS: We analyzed piRNA expression in osteoarthritis cartilage using the GEO database. To understand the impact of inflammatory factors on piRNA expression in chondrocytes, we conducted RT-qPCR experiments. We also investigated the effect of piRNA hsa_piR_019949 on chondrocyte proliferation using CCK-8 and clone formation assays. Furthermore, we assessed the influence of piRNA hsa_piR_019949 on chondrocyte apoptosis by conducting flow cytometry analysis. Additionally, we examined the differences in cartilage matrix composition through safranine O staining and explored the downstream regulatory mechanisms of piRNA using transcriptome sequencing. Lentiviral transfection of NEAT1 and NLRP3 was performed to regulate the metabolism of chondrocytes. RESULTS: Using RNA sequencing technology, we compared the gene expression profiles of 5 patients with osteoarthritis to 3 normal controls. We found a gene called hsa_piR_019949 that showed differential expression between the two groups. Specifically, hsa_piR_019949 was downregulated in chondrocytes when stimulated by IL-1ß, an inflammatory molecule. In further investigations, we discovered that overexpression of hsa_piR_019949 in vitro led to increased proliferation and synthesis of the extracellular matrix in chondrocytes, which are cells responsible for cartilage formation. Conversely, suppressing hsa_piR_019949 expression resulted in increased apoptosis (cell death) and degradation of the extracellular matrix in chondrocytes. Additionally, we found that the NOD-like receptor signaling pathway is linked to the low expression of hsa_piR_019949 in a specific chondrocyte cell line called C28/I2. Furthermore, we observed that hsa_piR_019949 can inhibit the expression of a long non-coding RNA called NEAT1 in chondrocytes. We hypothesize that NEAT1 may serve as a downstream target gene regulated by hsa_piR_019949, potentially influencing chondrocyte metabolism and function in the context of osteoarthritis. CONCLUSIONS: PiRNA hsa_piR_019949 has shown potential in promoting the proliferation of chondrocytes and facilitating the synthesis of extracellular matrix in individuals with osteoarthritis. This is achieved by inhibiting the expression of a long non-coding RNA called NEAT1. The implication is that by using hsa_piR_019949 mimics, which are synthetic versions of the piRNA, as a therapeutic approach, it may be possible to effectively treat osteoarthritis.

Changes in the small noncoding RNA transcriptome in osteosarcoma cells.

BACKGROUND: Osteosarcoma has the highest incidence among bone malignant tumors and mainly occurs in adolescents and the elderly, but the pathological mechanism is still unclear, which makes early diagnosis and treatment very difficult. Bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the sources of osteosarcoma cells. Therefore, a full understanding of the gene expression differences between BMSCs and osteosarcoma cells is very important to explore the pathogenesis of osteosarcoma and facilitate the early diagnosis and treatment of osteosarcoma. Small noncoding RNAs (sncRNAs) are a class of RNAs that do not encode proteins but directly play biological functions at the RNA level. SncRNAs mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), repeat RNAs and microRNAs (miRNAs). METHODS: In this study, we compared the expression of sncRNAs in BMSCs and osteosarcoma cells by high-throughput sequencing and qPCR and looked for differentially expressed sncRNAs. CCK-8, clone formation and transwell assay were used to detect the effect of sncRNA in MG63 cells. RESULTS: We found that 66 piRNAs were significantly upregulated and 70 piRNAs were significantly downregulated in MG63 cells. As for snoRNAs, 71 snoRNAs were significantly upregulated and 117 snoRNAs were significantly downregulated in MG63 cells. As for snRNAs, 35 snRNAs were significantly upregulated and 17 snRNAs were significantly downregulated in MG63 cells. As for repeat RNAs, 6 repeat RNAs were significantly upregulated and 7 repeat RNAs were significantly downregulated in MG63 cells. As for miRNAs, 326 miRNAs were significantly upregulated and 281 miRNAs were significantly downregulated in MG63 cells. Overexpression of piRNA DQ596225, snoRNA ENST00000364830.2, snRNA ENST00000410533.1 and miRNA hsa-miR-369-5p inhibited the proliferation and migration of MG63 cells. CONCLUSIONS: Our results provide a theoretical basis for the pathogenesis, early diagnosis and treatment of osteosarcoma.

The emerging role of snoRNAs in human disease.

Small nucleolar RNAs (snoRNAs) play critical roles in various biological processes. The aberrant expression or depletion of snoRNAs is related to various diseases. In previous research, most of the snoRNAs were categorized as C/D box snoRNAs and H/ACA box snoRNAs, whose typical functions were thought of as regulation of 2'-O-ribose methylation and pseudouridylation of ribosome RNAs, respectively. However, in the past two decades, studies have revealed an increasing number of snoRNAs without specific targets or determined cell functions. These findings indicated that some potential roles of snoRNAs are still unknown. Numerous studies have indicated the correlation of snoRNAs with human diseases. SnoRNAs play various roles in abundant biological processes, and they have great potential in controlling human diseases. This new and rising field could benefit from investigations of the disease pathogenesis, biomarker identification, and the determination of novel therapeutic targets. This review summarized the reports on snoRNAs and the regulation of different diseases in recent years.

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.

Microfluidic preparation of PLGA microspheres as cell carriers with sustainable Rapa release.

The current study, inspired by the immunosuppressive property of rapamycin (Rapa) and the benefit of microspheres both as drug delivery system and cell carriers, was designed to develop an efficient Rapa delivery system with tunable controllability to facilitate its local administration. A capillary-based two-phase microfluidic device was designed to prepare monodisperse poly(lactide-co-glycolide) (PLGA) microspheres to load Rapa (PLGA-Rapa-M). The physical and chemical properties of PLGA-Rapa-M were characterized, and the Rapa loading capacity and release profile were explored. Chondrocytes were chosen as a cell model to evaluate the adhesion and proliferation on these microspheres. Controllability over the microsphere properties was illustrated. The PLGA-Rapa-M is averagely 63.91 µm in size with a narrow size distribution and a CV of 2.44%. The encapsulation efficiency of Rapa within microspheres via the current microfluidics was around 98%, and Rapa loading could be easily varied with a maximum value of ∼20%. The PLGA-Rapa-M has a sustained Rapa release duration of ∼3 months. These microspheres could not only successfully be used for Rapa sustained release but also as cell carriers for cell therapy since they can support the attachment/proliferation of chondrocytes. Hence, improved therapeutic index could be expected by using the current developed Rapa-release system.

Reconstructing spinal dura-like tissue using electrospun poly(lactide-co-glycolide) membranes and dermal fibroblasts to seamlessly repair spinal dural defects in goats.

Many neuro- and spinal surgeries involving access to the underlying nervous tissue will cause defect of spinal dural mater, further resulting in cerebrospinal fluid leakage. The current work was thus aimed to develop a package which included two layers of novel electrospun membranes, dermal fibroblasts and mussel adhesive protein for repairing spinal dural defect. The inner layer is electrospun fibrous poly(lactide-co-glycolide) membrane with oriented microstructure (O-poly(lactide-co-glycolide)), which was used as a substrate to anchor dermal fibroblasts as seed cells to reconstitute dura-like tissue via tissue engineering technique. The outer layer is chitosan-coated electrospun nonwoven poly(lactide-co-glycolide) membrane (poly(lactide-co-glycolide)-chitosan). During surgery, the inner reconstituted tissue layer was first used to directly cover dura defects, while the outer layer was placed onwards with its marginal area tightly immobilized to the surrounding normal spinal dura aided by mussel adhesive protein. Efficacy of the current design was verified in goats with spinal dural defects (0.6 cm × 0.5 cm) in lumbar. It was shown that seamless and quick sealing of the defect area with the implants was realized by mussel adhesive protein. Guided tissue growth and regeneration in the defects of goats were observed when they were repaired by the current package. Effective cerebrospinal fluid containment and anti-adhesion of the regenerated tissue to the surrounding tissue could be achieved in the current animal model. Hence, it could be ascertained that the current package could be a favorite choice for surgeries involving spinal dural defects.

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.

Clinical and radiographic outcomes of cervical disc replacement with a new prosthesis.

BACKGROUND CONTEXT: Anterior cervical discectomy and interbody fusion was a classical treatment for cervical degenerative disc disease (CDDD). However, the rigid fusion also leads to a reduction in normal cervical spine motion and to increased biomechanical stress at adjacent levels, which in turn accelerates degenerative changes of the discs at these levels. Cervical disc replacement (CDR) is a new technology with the aim of addressing the limitations of fusion procession and preserving motion at the treated level. Discover prosthesis (DePuy Spine, Raynham, MA, USA) is a new type artificial disc and there are few reports about it. PURPOSE: The purpose of this study was to analyze the primary clinical and radiographic outcomes of CDR with Discover prosthesis to treat mono- or bi-segment CDDD in a Chinese population. STUDY DESIGN: The study design was prospective and single-center clinical trial of the Discover prosthesis in the treatment of patients with mono- or bi-segment CDDD. PATIENTS SAMPLE: Seventy-nine patients with 102 Discover prosthesis arthroplasty performed (56 mono-segment and 23 bi-segment) were evaluated. OUTCOME MEASURES: Clinical outcomes based on Japanese Orthopaedic Association (JOA), visual analog scale (VAS) pain score, and Odom's scale and radiographic outcomes including the anterior disc heights (ADH), posterior disc heights (PDH), range of motion, and performance of heterotopic ossification (HO) of the operative segment were assessed. METHODS: Clinical and radiographic follow-up was performed. Preoperative and postoperative ADH, PDH, and range of motion were measured from lateral and flexion-extension radiographs. The paired t test was used to assess the difference of clinical and radiographic outcomes before and after operation. The performance of HO was observed by two independent MD. RESULTS: The mean follow-up time for all the patients was 31.6 months, ranging from 24 to 43 months. Mean preoperative JOA score was 9.5, and VAS overall pain score was 7.2. At 2-, 6-, 12-, and 24-month follow-up, the mean JOA score was 14.1, 14.7, 15.3, and 14.9, whereas the mean VAS overall pain score was 1.9, 1.7, 1.8, and 1.4, respectively. Mean JOA and VAS scores showed statistical improvements in the postoperative period. Seven patients had mild dysphagia within the first month after operation. According to Odom's scale, 52 patients had excellent outcomes, 25 patients had good outcomes, and 2 patients had fair outcomes at 2-year follow-up. The Mean preoperative ADH and PDH of the operative segment were 4.9 mm and 3.1 mm. Compared with preoperative, there were significantly increased and maintenance well at 2- (7.5 mm, 5.1 mm), 6- (7.5 mm, 5.0 mm), 12- (7.4 mm, 4.9 mm) and 24-month (7.2 mm, 5.0 mm) follow-up. Range of motion of the operative segment in the postoperative follow-up was slightly increased than the preoperative follow-up but not statistically significant. Heterotopic ossification was presented in six replaced levels at 1-year follow-up including 4 Grade I and 2 Grade II and 18 replaced levels at the follow-up more than 2 years including 8 grade I and 10 grade II. No prosthesis subsidence or excursion was identified. CONCLUSIONS: The use of Discover prostheses in our study resulted in satisfactory clinical and radiographic outcomes. The prostheses can restore and maintain interbody height, while preserve the motion of the treated segment. Although the results of this study demonstrate initial safety and effectiveness in a Chinese population, we need further studies to know more about the impact of CDR with Discover prosthesis, especially on HO and adjacent segment degeneration.

Posterior hybrid technique for ossification of the posterior longitudinal ligament associated with segmental instability in the cervical spine.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To discuss the indications for a posterior hybrid technique for ossification of the posterior longitudinal ligament (OPLL) associated with segmental instability in the cervical spine and evaluate its effectiveness and safety. SUMMARY OF BACKGROUND DATA: Dynamic factors have been shown to play an important role in the progression of ossification and OPLL myelopathy. Laminoplasty has been widely used to treat cervical OPLL, but progressive kyphosis and progression of ossified lesions are often detected in long-term follow-up. METHODS: Fifteen patients were treated by a posterior hybrid technique including laminoplasty and lateral mass screw fixation at unstable levels. Preoperatively, the extent and type of OPLL, spinal cord compression, and presence of high-intensity zones were investigated by x-ray, computed tomography, and magnetic resonance imaging. Segmental instability in the cervical spine was investigated by dynamic x-ray. Postoperatively, clinical outcomes were evaluated with the Japanese Orthopedic Association scoring system and visual analog scale scores for neck pain. Radiologic results included cervical alignment and progression of OPLL. RESULTS: A total of 17 intervertebral levels in 15 patients (11 mixed-type and 4 continuous-type OPLL) had segmental instability, which was consistent with the presence of high-intensity zone levels in 10 (66.7%) patients. Neurological function as evaluated by the Japanese Orthopedic Association scores was significantly improved 6 months postoperatively and well maintained 4 years postoperatively. Neck pain was significantly improved 4 years postoperatively. No patients developed progressive kyphosis or progression of ossified lesions during the follow-up. Only 1 patient developed unilateral C5 palsy and completely recovered 2 months later. CONCLUSIONS: This hybrid posterior technique seems to be effective and safe in the treatment of selected patients with OPLL associated with segmental instability. The potential benefits of this technique include a stable environment for spinal cord recovery and prevention of progressive kyphosis and OPLL.

Association between osteoprotegerin genetic variants and osteoporosis in Chinese postmenopausal women.

The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of osteoprotegerin gene (OPG) with bone mineral density (BMD) and osteoporosis. A total of 338 Chinese postmenopausal women with primary osteoporosis and 367 healthy controls were enrolled. The lumbar spine (L2₋4), total hip and femoral neck hip of BMD were assessed by dual-energy X-ray absorptiometry (DEXA). OPG genetic variants were genotyped through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods. In this study, the g.18861A>G and g.25548C>T SNPs were detected and our data suggested that the significant differences of spine BMD, femoral neck hip BMD and total hip BMD were found among different g.18861A>G genotype, subjects with the AA genotype were significantly higher than those of AG and GG genotypes (p < 0.05). The g.25548C>T variant was not significantly associated with spine BMD, femoral neck hip BMD and total hip BMD (p > 0.05), while almost reached at the significant level in total hip BMD (p = 0.061). These findings suggeste that OPG gene variants are related to BMD and osteoporosis in Chinese postmenopausal women.

Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) gene +49G>A polymorphism was implicated to be associated with risk of malignant bone tumors, but the finding was inconclusive owing to the limited sample of a single study. The objective of the current study was to conduct a pooled analysis of four previously published studies to investigate the association between CTLA-4 +49G>A polymorphism and the risk of malignant bone tumors. Data were extracted, and the pooled odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was calculated to assess the association. Those four published studies included a total of 2,165 subjects. The pooled results indicated that CTLA-4 +49G>A polymorphism was significantly associated with risk of malignant bone tumors (AA versus GG: OR = 2.24, 95% CI 1.67-2.99, P < 0.001; AA/GA versus GG: OR = 1.35, 95% CI 1.14-1.61, P = 0.001; AA versus GG/GA: OR = 2.00, 95% CI 1.53-2.62, P < 0.001). Stratified analyses by tumor type showed that CTLA-4 +49G>A polymorphism was associated with risks of both osteosarcoma (AA versus GG: OR = 2.23, 95% CI 1.45-3.43, P < 0.001; AA/GA versus GG: OR = 1.35, 95% CI 1.04-1.75, P = 0.024; AA versus GG/GA: OR = 2.00, 95% CI 1.34-2.98, P = 0.001) and Ewing's sarcoma (AA versus GG: OR = 2.24, 95% CI 1.51-3.31, P < 0.001; AA/GA versus GG: OR = 1.36, 95% CI 1.07-1.72, P = 0.011; AA versus GG/GA: OR = 2.01, 95 % CI 1.39-2.89, P < 0.001). Therefore, results from the current pooled analysis suggest that CTLA-4 +49G>A polymorphism is associated with risk of malignant bone tumors, including osteosarcoma and Ewing's sarcoma.

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.

Current developments in dural repair: a focused review on new methods and materials.

The dura mater, the outermost layer of the meninges covering the brain and spinal cord, is a collagenous connective tissue consisting of numerous collagen fibers, fibroblasts, and few elastic fibers arranged in a parallel form. The dura mater may be damaged by trauma or excising during intracranial or spinal surgery., To date, cerebrospinal fluid leakage followed by dura damage is still an intractable complication due to its various secondary complications , dural repair has recently garnered increased attention with the progress of the spinal surgery and neurosurgery. In this review, we discuss commonly used methods including the addition of sealants, the use of substitutes, and other effective methods and materials.

Significance of segmental instability in cervical ossification of the posterior longitudinal ligament and treated by a posterior hybrid technique.

STUDY DESIGN: Retrospective cohort case study. OBJECTIVE: To evaluate significance of segmental instability (SI) in cervical ossification of the posterior longitudinal ligament (OPLL) myelopathy and effectiveness of a posterior hybrid technique in the treatment of OPLL associated with SI. Some studies suggested both static and dynamic compression factors accounted for the pathogenesis of myelopathy in the OPLL patients. METHOD: Between May 2005 and August 2007, 15 patients with multilevel cervical OPLL, diagnosed to be associated with SI, were treated by a posterior hybrid technique including laminoplasty and fusion at instable levels with lateral mass screw fixation. Another 15 cohort patients without SI treated by laminoplasty in the same period were included in the control group. Radiological and clinical data were compared between two groups. RESULTS: There were no significant differences in Preop. lordotic angle, extent of OPLL, type of OPLL and occupying rate, but more patients tended to present high-intensity zone (HIZ) on MRI in the group with SI. In 15 patients with SI, 17 intervertebral levels had SI, which were distributed at the noncontinuous levels of mixed-type OPLL or the adjacent levels of continuous-type OPLL. They were also consistent with the presence of HIZ levels in the major of patients. After operation, the lordotic angle was maintained well by the posterior hybrid technique in the OPLL with SI group, and was significantly greater than that in the OPLL without SI at the 3- and 4-year follow-up point. Postoperative kyphotic change of the cervical spine and postoperative progression of the ossified lesion were not observed in the OPLL with SI group, but they were respectively observed in four cases (26.7 %) and two cases (13.3 %) in the OPLL without SI group at the 4-year follow-up point. The preoperative C-JOA score in the OPLL with SI group was lower than that in the OPLL without SI group. The average C-JOA score and improvement rate were comparable in the first 2 years after operation between two groups, but there was a decrease in C-JOA score and improvement rate in the following 2 years in the OPLL without SI group. At the 3- and 4-year follow-up points, both postoperative C-JOA score improvement rate in the OPLL with SI group were superior to those in the OPLL without SI group. Each group had one case developing C5 palsy, but three cases in the OPLL without SI group developed late neurological deterioration due to postoperative kyphotic change or progression of the ossified lesion. CONCLUSIONS: Segmental instability, a degenerative dynamic factor, is important to the OPLL myelopathy. The posterior hybrid technique seemed to be effective and safe in the treatment of selective OPLL patients associated with SI. The benefits may include providing stabilization environment for spinal cord recovery, and preventing progressive kyphotic change and progression of OPLL.

[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.

Development of mesenchymal stem cell-implant complexes by cultured cells sheet enhances osseointegration in type 2 diabetic rat model.

This study investigated the hypothesis that a mesenchymal stem cells (MSC)-implant complex could be used in type 2 diabetic rats. Diabetes was modeled with type 2 diabetic rats induced by high fat diet with low dose streptozotocin (STZ) injected intraperitoneally. MSC sheets were harvested from culture flasks, wrapped around implants to construct the complexes, and then cultured in an osteogenic medium. The layered cell sheets integrated well with the implants and remained viable, with small mineralized nodules visible on the implant surfaces after culturing. The MSC-implant complexes were inserted into the right tibiae of the diabetic rats. Titanium implants served as controls. After four and eight weeks of healing, the tibiae were observed via MicroCT and harvested for histological examination. For the MSC-implant complexes, MicroCT analysis showed that bone volume ratio and trabecular thickness increased significantly (p<0.05), and trabecular separation decreased significantly (p<0.05) compared to the titanium implants in diabetic rats. Histological examination revealed a greater amount of new bone tissue forming around the MSC-implant complexes and a higher bone implant contact (BIC) rate than the titanium implants. These findings demonstrate that MSC-implant complexes possess osteogenic abilities and can be used in diabetic rats to improve the BIC rate. Thus, MSC-implant complexes provide a novel tissue engineering approach that promotes osseous healing and may potentially be useful in the treatment of diabetic patients.

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.