Yongfei Guo

MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow- Derived Mesenchymal Stem Cells by Targeting HOXA10

Background/Aims: Human bone marrow-derived mesenchymal stem cells (hMSCs) are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts. The bone morphogenetic protein-inducible gene homeobox a10 (HOXA10) is a critical regulator of osteogenesis. The objective of the present study was to identify microR-NAs (miRNAs) targeting HOXA10 and examine the effects on the osteogenic differentiation of hMSCs. Methods: Based on in silico analysis, HOXA10-targeting miRNAs were selected and their regulatory roles in osteoblast differentiation were investigated. Results: Six HOXA10-targeting miRNAs were identifIed by computational analysis, of which miR-320a was selected for further analysis because it was downregulated during osteogenic induction. Overexpression of miR-320a downregulated HOXA10 and significantly inhibited osteogenesis in hMSCs, as determined by the downregulation of the osteogenic markers Runx2, ALP, and OC and the inhibition of ALP activity and matrix mineralization, whereas miR-320a inhibition had the opposite effects. Furthermore, ectopic expression of HOXA10 (not including 3′-UTR) rescued the effects of miR-320a on osteogenic differentiation. Conclusion: These results suggest that miR-320a acts as a critical regulator of osteogenic differentiation of hMSCs by repressing its target HOXA10.

Study design: in vitro and in vivo assessment of bone morphogenic protein 2 combined with platelet-rich plasma on treatment of disc degeneration

ObjectiveOur aim was to investigate the biological effects of bone morphogenic protein 2 (BMP2) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocyte-like cells in platelet-rich plasma (PRP) gel in vitro. In addition, the effectiveness of BMP2-transduced BMSCs in combined with PRP gel to repair the degenerated intervertebral disc in a rabbit model was also evaluated.Summary of background dataPrevious studies have shown that tissue engineering provides many promising advantages to treating disc degeneration and may reverse the pathological process of disc degeneration.MethodsThe expressions of types I, II and X collagen, aggrecan and Sox9 of the BMP2-transduced BMSCs in monolayer or PRP gel were examined by reverse transcriptase polymerase chain reaction (RT-PCR). Sixty New Zealand white rabbits were divided into five groups: 12 normal controls; 12 puncture operated with only disc degeneration being induced; 12 PRP transplantation animals; 12 BMSC and PRP-transplantation animals; 12 BMP2-transduced BMSCs and PRP-transplantation animals. The effect of BMP2-transduced BMSCs on degenerated discs were evaluated by magnetic resonance image (MRI) scan, histology, immunohistochemistry and Western blot analysis.ResultsBMP2 could facilitate chondrogenic differentiation of BMSCs in monolayer or PRP gel. The discs treated with BMP2-transduced BMSCs exhibited relatively well-preserved nucleus pulposus (NP) structure. Significantly higher T2-weighted signal intensity and a greater amount of extracellular matrix were observed in the BMP2-transduced BMSC group compared with other groups. In addition, the presences of BMP2-transduced BMSCs were identified at week 12 postoperatively in vivo.ConclusionsBMP2-transduced BMSCs can maintain the chondrocyte-like phenotype in PRP gel in vitro, and the combined use of these two agents can significantly promote repair of the degenerated discs in vivo.

Connexin 43 Affects Osteogenic Differentiation of the Posterior Longitudinal Ligament Cells via Regulation of ERK Activity by Stabilizing Runx2 in Ossification.

Aims: Connexin 43 is one of the most potent gap junction proteins related to osteoblast differentiation and bone formation. We hypothesized that Connexin 43 is a significant factor in osteogenic differentiation in the posterior longitudinal ligament through the regulation of extracellular signal-regulated kinases (ERK) activity by converging on Runt-related transcription factor 2 (Runx2) activity. In this study, we mapped the activity of Connexin 43 to ERK and Runx2 by extracting longitudinal ligament cell for culture and silencing Connexin expression in addition to dexamethasone treatment in vitro. Methods: qRT-PCR, Western Blot, and Runx2-responsive Luciferase Reporter Assay were performed to detect the activity of ERK, Runx2 and the expression levels of osseous genes under Connexin 43 modification. Results: Downregulation of Connexin 43 resulted in suppression of dexamethasone-induced osteogenic differentiation, inhibition of the ERK and Runx2 activity, and reduction of osseous gene expression. Conclusion: these data support that Connexin 43 significantly regulates osteogenic differentiation in the cells from posterior longitudinal ligament by altering the activity of ERK, and subsequently causing the modification of Runx2.

Surgical Incision and Approach in Thoracolumbar Extreme Lateral Interbody Fusion Surgery: An Anatomic Study of the Diaphragmatic Attachments.

Study Design. Cadaveric study. Objective. To provide anatomical basis for deciding the surgical approach and skin incision in thoracolumbar extreme lateral interbody fusion (XLIF) by delineating the attachment points of diaphragm. Summary of Background Data. Although the general anatomy of the thoracic diaphragm is well described, the specific attachment points of diaphragm concerned with the XLIF approach is yet to be elaborated. Methods. Dissections were performed on 21 cases of formalin fixed specimens (12 males, 9 females, a total of 42 sets of data). Special attention was paid to the attachment points of diaphragm on both sides at the midaxillary line (MAL point) and the vertebral level parallel to the MAL point (VL-MAL). The attachment points of diaphragm on the front and back edge of the spinal column (FES point and BES point) were also described. Results. The MAL point of diaphragm muscle lied between the inferior edge of the 10th rib and the superior edge of the 12th rib (20 out of 21 on left, 21 out of 21 on right). VL-MAL lied between L1 and L2 vertebrae level (20 out of 21 on left, 18 out of 21 on right). The attachments on both sides of the vertebral column mainly located between the upper edge of T12 vertebrae and L1-L2 disc (38 out of 42). Conclusion. A transthoracic approach should be considered when the target level was above T12 vertebrae, whereas a retroperitoneal approach should be chosen when target level was below L1-L2 disc. If the target level is located between T12 and L1-L2 disc, whether via transthoracic, retropleural, or retroperitoneal approach should be determined according to the conditions of patients and the skill and experience of the surgeon. Incision should be made above the 10th rib for the transthoracic approach and below the 12th rib for the retroperitoneal approach. Level of Evidence: 4

Ossification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway

Ossification of the posterior longitudinal ligament (OPLL) involves ectopic calcification of the spinal ligament preferentially at the cervical spine. OPLL is associated with different diseases and occurs by endochondral ossification, which is associated with the activity of different transcription factors. However, the pathogenesis of OPLL remains unclear. Here, we investigated the role of osterix (Osx), a transcription factor that functions downstream of Runx2 and is an important regulator of osteogenesis, in the process of OPLL in a dexamethasone (Dex)-induced model of spinal ligament ossification. Our results showed that Osx is upregulated in patients with OPLL and during the ossification of ligament cells in parallel with the upregulation of osteogenic markers including osteocalcin (OCN), alkaline phosphatase (ALP) and collagen-1 (Col-1). Dex-induced ossification of ligament cells was associated with the downregulation and inactivation of β-catenin, and these effects were offset by Osx knockdown. Activation of β-catenin signaling abolished the effect of Dex on ossification and the upregulation of osteogenic markers. Taken together, our results suggest that OPLL is mediated by Osx via a mechanism involving the Wnt/β-catenin signaling pathway, providing a basis for further research to identify potential targets for the treatment of OPLL.

In Situ Decompression to Spinal Cord During Anterior Controllable Antedisplacement Fusion Treating Degenerative Kyphosis with Stenosis: Surgical Outcomes and Analysis of C5 Nerve Palsy Based on 49 Patients

OBJECTIVEnTo observe outcomes of anterior controllable antedisplacement fusion (ACAF) in treatment of degenerative kyphosis with stenosis (DKS) and analyze probability of C5 nerve palsy.nnnMETHODSnFrom 2016 to 2017, a consecutive cohort of adults with DKS underwent ACAF. All patients underwent cervical radiography, computed tomography, and magnetic resonance imaging. Operative duration, blood loss, and hospital stay were estimated. Radiologic assessment included kyphotic correction, decompression width, and spinal canal area. Postoperative curvature of spinal cord was observed on sagittal magnetic resonance imaging. Japanese Orthopaedic Association score was used to evaluate neurologic status. C5 nerve palsy and other complications were recorded.nnnRESULTSnThe study included 49 patients. There was significant kyphosis correction postoperatively (-19.4° vs. 3.5°, P < 0.01). On cross-sectional computed tomography, mean decompression width was 19.0 mm, and spinal canal area was 218.5 mm2. On sagittal magnetic resonance imaging, spinal cord curvature was classified into 5 types: type I, lordosis; type II, straight with no shifting; type III, straight with shifting; type IV, sigmoid; and type V, kyphosis. After ACAF, the spinal cord was maintained in good curvature with no shifting in all patients. No patient presented with C5 nerve palsy. Mean postoperative Japanese Orthopaedic Association score was significantly better than preoperatively (14.9 points vs. 9.0 points, P < 0.01), with mean improvement rate of 79.8%.nnnCONCLUSIONSnACAF provides in situ decompression and good curvature to the spinal cord. Good neurologic recovery is obtained with lower incidence of C5 nerve palsy when ACAF is used to treat DKS.

Anterior Controllable Antedisplacement Fusion (ACAF) for Severe Cervical Ossification of the Posterior Longitudinal Ligament: Comparison with Anterior Cervical Corpectomy with Fusion (ACCF)

OBJECTIVEnAnterior cervical corpectomy and fusion (ACCF), in which a ventral constriction is resected, can decompress myelopathy and is considered the optimal treatment for ossification of the posterior longitudinal ligament (OPLL) up to now. However, its disadvantages are incomplete decompression, high surgery- and implant-related complication rates, and extremely surgical technique demanding. Our object was to introduce anterior controllable antedisplacement fusion (ACAF), a new surgical technique to treat OPLL, and compare it with ACCF.nnnMETHODSnACAF was performed on 34 patients with spinal stenosis with myelopathy due to severe (occupying rate ≥50%) OPLL. Pre- and postoperatively, we measured decompression width and spinal canal area on cross-sectional computed tomography and morphology and anteroposterior diameter of the spinal cord at the most severely affected segment on cross-sectional magnetic resonance imaging and cross-sectional computed tomography. Japanese Orthopedic Association scoring was used to evaluate neurologic status. The ACAF group and a control group of 36 patients with ACCF were compared.nnnRESULTSnPostoperatively, decompression width (17.9 ± 1.0 vs. 15.1 ± 0.8 mm; P < 0.01), spinal canal area (150.4 ± 31.6 vs. 127.0 ± 27.0 mm2; P < 0.01), and anteroposterior spinal cord diameter (5.4 ± 0.6 vs. 5.0 ± 1.1 mm; P < 0.05) were significantly greater in the ACAF group. At 6 months,xa0mean Japanese Orthopedic Association score was significantly better in the ACAF group (15.4 ± 0.9 vs. 14.5 ± 2.5 points; Pxa0= 0.04).nnnCONCLUSIONSnACAF, providing adequate decompression of the spinal cord and good outcomes, is a well choice in the treatment of spinal stenosis due to severe OPLL.

A Comparative Study Between Anterior Controllable Antedisplacement and Fusion Versus Laminoplasty in the Surgical Management of Multilevel Cervical Ossification of the Posterior Longitudinal Ligament

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Quantitative Anterior Enlargement of the Spinal Canal by Anterior Controllable Antedisplacement and Fusion for the Treatment of Cervical Ossification of the Posterior Longitudinal Ligament with Myelopathy

PURPOSEnThis retrospective study aimed to investigate the effect of quantitative enlargement of spinal canal by anterior controllable antedisplacement and fusion (ACAF) for cervical ossification of the posterior longitudinal ligament (OPLL).nnnMETHODSnForty-three patients with OPLL who underwent ACAF were enrolled. According to the use of a curvature ruler (CR), patients were divided into group A (CR used, nxa0= 21) and group B (CR not used, nxa0= 22). The average follow-up was 9.5 months. The occupation rate (OR) of the spinal canal and the curvature of the cervical plate were recorded. The Japanese Orthopedic Association (JOA) scores were analyzed, and the recovery rate (RR) was calculated. Surgical complications were also investigated.nnnRESULTSnThe OR of the spinal canal in group A decreased from 66.7% ± 12.8% to 19.1% ± 10.9% after surgery (P < 0.05). In group B, the preoperative and postoperative OR was 63.9% ± 11.7% and 21.2% ± 8.7%, respectively (P < 0.05). Patients in group A had higher agreement of the curvature of the cervical plate between preoperative planning and postoperative measurement. The RR of JOA scores in group A was 73.7% ± 19.7%, higher than in group B (70.9% ± 7.3%, Pxa0>xa00.05). Further comparison between the 2 groups, excluding those patients with OR <50%, showed that both JOA score and RR in group A were higher than in group B at the final follow-up (P < 0.05).nnnCONCLUSIONSnThe quantitative enlargement of the spinal canal by ACAF may provide a positive and favorable effect on enlarging the spinal canal and achieving better neurologic recovery for the treatment of cervical OPLL with myelopathy. CR can facilitate the achievement of better and more quantitative spinal canal enlargement.

New Technology for Surgical Treatment of Osteoporotic Vertebral Compression Fractures: The Transvertebral Bone Graft and Fixation

OBJECTIVEnTo introduce an innovative surgical technique, transvertebral bone graft and augmentation (TBGA), to and evaluate its clinical efficacy in treating osteoporotic vertebral body compression fractures (VCFs), with balloon kyphoplasty (BKP) as a control.nnnMETHODSnA total of 81 patients with a single-level osteoporotic VCF underwent TBGA (nxa0= 38) or BKP (nxa0= 43) at our hospital between October 2012 and January 2015. The average duration of follow-up period was 27.9 months. The patients were evaluated with plain radiography, computed tomography, and magnetic resonance imaging preoperatively, immediately postoperatively, at 3- and 6-month follow-ups, and every 6 months thereafter. Clinical status was assessed using the Oswestry Disability Index (ODI) and a visual analog scale (VAS). In addition, parameters of anterior vertebral body height (AVBH), kyphosis angle (KA), adjacent segment degeneration (ASD), and complications were also compared between the 2 groups.nnnRESULTSnSignificant clinical improvements in ODI, VAS scores, AVBH, and KA were seen in both the TBGA and BKP groups after surgery (P < 0.05). However, the differences in improvements in ODI and VAS between the TBGA and BKP groups were not statistically significant (P > 0.05). The improvements in AVBH and KA were significantly better in the TBGA group (P < 0.05). Furthermore, the rates of ASD and complications were significantly lower in the TBGA group during the follow-up period (P < 0.05).nnnCONCLUSIONSnTBGA is an effective and safe surgical technique that appears to be a promising alternative to BKP for the surgical treatment of osteoporotic VCFs.