Search

Mesenchymal stem cells (MSCs) are one of the attractive candidates in regenerative medicine of many clinical applications because of their low immunogenicity and immunomodulatory property. Our previous studies provided that mouse bone marrow-derived Sca-1+MSCs could drive the differentiation of regulatory DC (regDCs) (Scal-1+ BM-MSC-driven DC [sBM-DCs]) from hemopoietic progenitor cells (HPCs) and the Notch pathway played a critical role in maintaining the immunomodulatory property. However, the detailed mechanisms of their immunoregulatory capacity are not fully defined. In the present study, we show that BM-MSCs expressed high levels of Jagged 1 while sBM-DCs expressed high levels of Notch1. Jagged1 expressed on the surface of BM-MSCs initiated Notch signaling to maintain the immunomodulatory property of the sBM-DCs. The level of TGF-β is high in MSCs, either alone or coculture with HPCs medium. TGF-β plays a vital role in the proliferation and differentiation of sBM-DCs and inhibition of TGF-β reduce the number and increase the percentage of CD34, CD117, CD135 of generation cells. Thus, MSCs induced the regDCs from HPCs via the Notch signaling pathway and TGF-β synergistically. This study further broadens our understanding of the immunomodulatory mechanism and the potential therapeutic efficacy of MSCs.

Background To assess the risk factors for blood transfusion in a great number of adolescent cases with different types of scoliosis who received scoliosis surgery. Methods Data of patients who were diagnosed as scoliosis and received one-stage posterior correction and spinal fusion from January 2014 to December 2017 were prospectively collected and retrospectively analyzed. Patients’ demographic characteristics, segments of spinal fusion, Cobb angle of the major curve,osteotomy pattern, preoperative and postoperative levels of hemoglobin, and allogeneic blood transfusion (ABT) were recorded and analyzed. Results In this study, 722 cases with adolescent scoliosis were included, of whom 32.8% (237/722) received ABT. Risk factors included diagnosis: neurofibromatosis (OR = 5.592), syndromic (OR = 3.029),osteotomy: Ponte osteotomy (OR = 5.997), hemivertebrae resection (OR = 29.171), pedicle subtraction osteotomy (PSO)(OR = 8.712), vertebral column resection (VCR)(OR = 32.265);fusion segments (OR = 1.224) and intraoperative blood loss (OR = 1.004). In the subgroup analysis of cases with idiopathic scoliosis, Ponte osteotomy (OR = 6.086), length of segments of spinal fusion (OR = 1.293), and intraoperative blood loss (OR = 1.001) were found as risk factors for ABT. Results of receiver operating characteristic (ROC) curve analysis revealed that length of segments of spinal fusion equal to 11.5 vertebrae was the best cutoff value for cases with idiopathic scoliosis who did not receive osteotomy in both ABT group and non-ABT group. In the subgroup analysis of congenital scoliosis, Ponte osteotomy (OR = 5.087), hemivertebra resection (OR = 5.457), PSO (OR = 4.055), VCR (OR = 6.940), and intraoperative blood loss (OR = 1.004) were risk factors for ABT. Conclusions Method of diagnosis, osteotomy pattern, segments of spinal fusion, and intraoperative blood loss were risk factors for ABT in cases with adolescent scoliosis. In cases with idiopathic scoliosis, Ponte osteotomy and segments of spinal fusion longer than 11.5 vertebrae were risk factors for ABT. In cases with congenital scoliosis, osteotomy pattern was the main risk factor for ABT. Level of evidence Level III.

Background/aims An increasing body of evidence has demonstrated that long non-coding RNAs (lncRNAs) play a vital regulatory role in intervertebral disk degeneration (IVDD). Nucleus enriched abundant transcript 1 (NEAT1), a novel cancer-related lncRNA, is associated with many malignancies, including ovarian cancer, and esophageal squamous cell carcinoma. Nevertheless, the role of NEAT1 in the progression of IVDD remains to be studied. Here, we explored the effect of NEAT1 on the progression of IVDD and the mechanisms involved. Methods An IVDD model was constructed in SD rats in vivo, and degeneration was induced by advanced glycation end product (AGE) in human nucleus pulposus cells (HNPC) in vitro. Quantitative real-time PCR was performed to detect the relative NEAT1 and miR-195a expressions and further confirmed the relationship between NEAT1 and miR-195a. Cell apoptosis was evaluated by TUNEL assay. The related mechanisms were explored by Western blot assay. Results The relative NEAT1 expression was significantly upregulated in the IVDD rat model and the denatured HNPC. Silencing of NEAT1 expression in HNPC significantly promoted the Collagen II and TIMP-1 expression induced by AGE while greatly suppressing the expressions of MMP-3 and cleaved caspase-3. Besides, downregulation of NEAT1 obviously reversed the AGE-induced apoptosis in HNPC. More interestingly, these effects of NEAT1 knockout on HNPC were largely reversed by silencing of miR-195a or overexpression of BAX under the AGE treatment. Mechanically, the direct combination of NEAT1 with miR-195a resulted in upregulation of MMP-3, cleaved caspase-3, BAX, and BAK, as well as downregulation of Collagen II and TIMP-1, which are associated with EMT and apoptosis. We also demonstrated similar results in the in vivo experiments. Conclusion NEAT1 played its role in IVDD progression via partly by mediating the miR-195 expression and might be used as a potential target for IVDD therapy.

The mechanism of steroid-associated femoral head necrosis remains unclear. The present study investigated the role of microRNA-23a-3p (miR-23a-3p) in the incidence of osteonecrosis in a rat model. An miR-23a-3p mimic, an inhibitor and a negative control were transfected into bone mesenchymal stem cells using a lentiviral vector, and then injected into the steroid-induced femoral head necrosis model. Osteonecrosis incidence was assessed by micro computed tomography and histopathology. Low-density lipoprotein receptor-related protein 5 (LRP-5) expression was assessed by immunohistochemistry. The results demonstrated the incidence of osteonecrosis decreased in the miR-23a-3p inhibitor group compared with the miR-23a-3p mimic group (18.2% vs. 75%; P

Nuclear receptor subfamily 4 group A member 1 (NR4A1)-induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor-α (TNF-α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP-activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF-α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin-related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening-related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F-actin homeo-stasis. Inhibiting NR4A1 attenuated TNF-α and CHX-induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening-related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1-mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening-induced cell death and F-actin-related migratory inhibition.

Background The optimal treatment of Lenke 5C curves in adolescent idiopathic scoliosis is still unclear. Objective To compare the outcomes and the spontaneous correction behavior between anterior and posterior selective fusion techniques in a large case series. Methods Demographic and surgical data for patients with Lenke 5C curves treated with anterior or posterior fusion were collected from July 2002 to September 2011. Clinical assessment and radiographic parameters were compared preoperatively and postoperatively and at a minimum of 2 years of follow-up. Results Fifty-three Lenke 5C adolescent idiopathic scoliosis cases with an average follow-up of 4 years (range, 2-9.6 years) were included. The clinical scores were similar between the 2 groups. Postoperative major thoracic curvature changes were similar. The minor thoracic curve demonstrated a higher spontaneous correction rate in the posterior group. At follow-up, the minor thoracic curve showed a greater loss of correction in the posterior group, and finally both groups were comparable. Surgical time, intraoperative blood loss, and complications were comparable. A total of 5 patients had a final thoracic curve larger than the preoperative degrees. Conclusion Selective fusion of the major thoracolumbar/lumbar curve in Lenke 5C adolescent idiopathic scoliosis can be achieved by anterior and posterior techniques. The spontaneous correction of the unfused thoracic curve was comparable after an average of 4 years follow-up.

Background In total knee arthroplasty (TKA), handling of the patella surface is still quite controversial. We carried out a prospective randomized study to compare circumpatellar electrocautery plus patella resurfacing vs circumpatellar electrocautery only in the single-staged bilateral TKA in Chinese population. Methods One hundred five patients diagnosed with late-staged osteoarthritis who received single-staged bilateral TKA were screened and 53 patients were included. All patients received the same posterior cruciate-stabilizing total knee prostheses. Patients were randomized to receive circumpatellar electrocautery plus patellar resurfacing or circumpatellar electrocautery only for the first TKA, and the second knee received the opposite treatment. All patients were followed for a minimum of 2 years. Results No differences were found with regard to Knee Society Score, Feller score, anterior knee pain, and revision rates. Fifty-two percent of patients had no preference with regard to pain and function, 27% of patients preferred the resurfacing plus circumpatellar electrocautery knee while 21% of the patients preferred the circumpatellar electrocautery only knee. The Insall-Salvati index and the patella tilt were a little smaller in the resurfacing group. One patient (2.1%) in the circumpatellar electrocautery group underwent a patella resurfacing revision for severe anterior knee pain and patella subluxation. Conclusion Equivalent clinical results for circumpatellar electrocautery plus resurfacing and circumpatellar electrocautery alone of the patella in TKA were demonstrated in selective Chinese population with thick enough patella.