Baichuan Wang

Functionalized self-assembling peptide nanofiber hydrogel as a scaffold for rabbit nucleus pulposus cells.

In this study, a new functionalized peptide RLN was designed containing the bioactive motif link N, the amino terminal peptide of link protein. A link N nanofiber scaffold (LN-NS) was self-assembled by mixing peptide solution of RLN and RADA16. The characterization of LN-NS was tested using atomic force microscopy (AFM). The biocompatibility and bioactivity of this nanofiber scaffold for rabbit nucleus pulposus cells (NPCs) were also evaluated. This designer functionalized nanofiber scaffold exhibited little cytotoxicity and promoted NPCs adhesion obviously. In three-dimensional cell culture experiments, confocal reconstructed images testified that the functionalized LN-NS-guided NPCs migration from the surface into the hydrogel considerably, in which the RADA16 scaffold did not. Moreover, the functionalized LN-NS significantly stimulated the biosynthesis of extracelluar matrices (ECM) by NPCs. Our findings demonstrate that the functionalized nanofiber scaffold containing link N had excellent biocompatibility and bioactivity with rabbit NPCs and could be useful in the nucleus pulposus regeneration.

Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS) containing N-terminal peptide sequence of link protein (link N) can promote nucleus pulposus cells (NPCs) adhesion and three-dimensional (3D) migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs), a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration.

High Birth Weight Increases the Risk for Bone Tumor: A Systematic Review and Meta-Analysis

There have been several epidemiologic studies on the relationship between high birth weight and the risk for bone tumor in the past decades. However, due to the rarity of bone tumors, the sample size of individual studies was generally too small for reliable conclusions. Therefore, we have performed a meta-analysis to pool all published data on electronic databases with the purpose to clarify the potential relationship. According to the inclusion and exclusion criteria, 18 independent studies with more than 2796 cases were included. As a result, high birth weight was found to increase the risk for bone tumor with an Odds Ratio (OR) of 1.13, with the 95% confidence interval (95% CI) ranging from 1.01 to 1.27. The OR of bone tumor for an increase of 500 gram of birth weight was 1.01 (95% CI 1.00–1.02; p = 0.048 for linear trend). Interestingly, individuals with high birth weight had a greater risk for osteosarcoma (OR = 1.22, 95% CI 1.06–1.40, p = 0.006) than those with normal birth weight. In addition, in the subgroup analysis by geographical region, elevated risk was detected among Europeans (OR = 1.14, 95% CI 1.00–1.29, p = 0.049). The present meta-analysis supported a positive association between high birth weight and bone tumor risk.

The synergistic anticancer effect of cisplatin combined with Oldenlandia diffusa in osteosarcoma MG-63 cell line in vitro.

Background Oldenlandia diffusa (OD) is a well-known traditional Chinese medicine, which is used to prevent and treat many disorders, especially cancers. However, its role in osteosarcoma has not been well understood. Here, we used OD and cisplatin individually and combined in osteosarcoma MG-63 cell to explore whether OD could induce cellular apoptosis and suppress the ability of proliferation and invasion of osteosarcoma MG-63 cell. Methods The changes of cellular shape were analyzed by optical microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay was used to analyze cell survival rate in vitro. Flow cytometry was performed to detect cell cycle and cell death. Scratch migration assay was used to evaluate cell migration and invasion. Western blot was performed to determine the expression levels of pro-apoptotic and anti-apoptotic protein. Results In this study, we found that the survival rate reduced significantly in the combined group compared with the individual group and control group. The apoptosis-inducing effect of combined application was much more significant than that of individual application. The invasion ability of combined application was significantly lower than that of the individual application. In the combined group, there were high expression levels of pro-apoptotic protein and low expression of anti-apoptotic protein. Cell-cycle analysis showed a change in the cell-cycle distribution and arrested cells in G2-M phase. Conclusion In this study, we found that OD inhibited proliferation and induced apoptosis in the human osteosarcoma MG-63 cell line in a time-dependent and dose-dependent manner. In addition, OD displayed inhibitory activity on MG-63 cell proliferation and invasion and the study also showed that OD activity might be mediated by caspase activation. These data suggest that OD might represent a novel, efficient candidate agent for further experimentation in osteosarcoma treatment.

Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

Compression-induced programmed cell death of nucleus pulposus (NP) cells is an important contributor to intervertebral disc degeneration (IDD). Dynamin-related protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed necrosis upon cellular injury. However, limited information is available about the role of Drp1 in compression-induced programmed necrosis of NP cells. In the present study, we found that compression resulted in upregulation and mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of NP cells treated with compression. Furthermore, Drp1 promoted mitochondrial translocation of p53 and nuclear translocation of apoptosis-inducing factor (AIF) in compression-treated NP cells. Inhibition of p53 mitochondrial translocation by pifithrin-μ (PFT-μ) and silencing of AIF expression by siRNA significantly alleviated compression-induced NP cell programmed necrosis. These data indicates that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.

Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells

Aims: Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression‐induced damage in rat nucleus pulposus (NP) cells. Materials and methods: Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca2 +]i) were determined by fluorescent probes DCFH‐DA, JC‐1 and Fluo‐3/AM, respectively. Apoptosis‐related proteins (cleaved caspase‐3, cytosolic cytochrome c, Bax and Bcl‐2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Key findings: Edaravone attenuated the compression‐induced decrease in viability of NP cells in a dose‐dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression‐induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression‐induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca2 +]i. In addition, edaravone promoted the expression of aggrecan and collagen II in compression‐treated NP cells. Significance: These results strongly indicate that edaravone ameliorates compression‐induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD.

Palliative Surgery in Treating Painful Metastases of the Upper Cervical Spine: Case Report and Review of the Literature.

AbstractIncreased incidence of upper cervical metastases and higher life expectancy resulted in higher operative rates in patients. The purpose of this study was to explore the methods and the clinical outcomes of palliative surgery for cervical spinal metastases.A systematic review of a 15-case series of upper cervical metastases treated with palliative surgery was performed. All cases underwent palliative surgery, including anterior tumor resection and internal fixation in 3 cases, posterior tumor resection and internal fixation in 10 cases, and combined anterior and posterior tumor resection and internal fixation in 2 cases. Patients were followed-up clinically and radiologically after the operation, and visual analog scale (VAS) and activities of daily living scores were calculated. In addition, a literature review was performed and patients with upper cervical spine metastases were analyzed.The mean follow-up period was 12.5 months (range, 3–26 months) in this consecutive case series. The pain was substantially relieved in 93.3% (14/15) of the patients after the operation. The VAS and Japanese Orthopedic Association scores showed improved clinical outcomes, from 7.86 ± 1.72 and 11.13 ± 2.19 preoperatively to 2.13 ± 1.40 and 14.26 ± 3.03 postoperatively, respectively. The mean survival time was 9.5 months (range, 5–26 months). Dural tear occurred in 1 patient. Wound infections, instrumentation failure, and postoperative death were not observed. Among our cases and other cases reported in the literature, 72% of the patients were treated with simple anterior or posterior operation, and only 12% of the patients (3/25) underwent complex combined anterior and posterior operation.Metastatic upper cervical spine disease is not a rare occurrence. Balancing the perspective of patients on palliative surgery concerning the clinical benefits of operation versus its operative risks can assist the decision for surgery.

Effect of a synthetic link N peptide nanofiber scaffold on the matrix deposition of aggrecan and type II collagen in rabbit notochordal cells

Self-assembling peptide nanofiber scaffolds have been studied extensively as biological materials for 3-dimensional cell culture and repairing tissue defects in animals. However, few studies have applied peptide nanofiber scaffolds in the tissue engineering of intervertebral discs (IVDs). In this study, a novel functionalized peptide scaffold was specifically designed for IVD tissue engineering, and notochordal cells (NCs) as an alternative cell source for IVD degeneration were selected to investigate the bioactive scaffold material. The novel RADA16-Link N self-assembling peptide scaffold material was designed by direct coupling to a bioactive motif link N. The link N nanofiber scaffold (LN-NS) material was obtained by mixing pure RADA16-I and RADA16-Link N (1:1) designer peptide solutions. Although live/dead cell assays showed that LN-NS and RADA16-I scaffold materials were both biocompatible with NCs, the LN-NS material significantly promoted NC adhesion compared with that of the pure RADA16-I SAP scaffold material. The depositions of aggrecan and type II collagen, which are significant markers for IVD cells, were remarkably increased. Furthermore, the results indicated that the link N motif, the matrix analog of the nucleus pulposus, significantly promoted the accumulation of other extracellular matrices in vitro. We conclude that the novel LN-NS material is a promising biological scaffold material, and may have a broad range of applications in IVD tissue engineering.

Downregulation of DEPTOR inhibits the proliferation, migration, and survival of osteosarcoma through PI3K/Akt/mTOR pathway

Accumulating evidence reveals that DEP-domain containing mTOR-interacting protein (DEPTOR) plays pivotal roles in the pathogenesis and progression of many tumors. However, the expression level of DEPTOR and its function in the tumorigenesis of osteosarcoma (OS) remain unknown. In this study, we conducted quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry to detect DEPTOR expression level in human OS tissues and cell lines. To assess DEPTOR function, DEPTOR siRNA was designed and transfected into OS cells, which were then used in a series of in vitro assays. Our results indicated that DEPTOR was highly expressed in some OS tissues and cell lines. DEPTOR knockdown by siRNA dramatically inhibited cell proliferation, migration, invasion, and the formation of vasculogenic mimicry in OS cells. In addition, DEPTOR knockdown induced cell cycle arrest in the G0/G1 phase and apoptosis in the OS cell lines, MG63 and MNNG/HOS. Furthermore, we found that DEPTOR knockdown notably activated mTOR and inhibited the PI3K/Akt pathway. Taken together, these results suggest that DEPTOR overexpression is necessary for the proliferation, migration, invasion, formation of vasculogenic mimicry, and survival of OS cells and may be a potential target for the treatment of OS.

What are the Functional Results, Complications, and Outcomes of Using a Custom Unipolar Wrist Hemiarthroplasty for Treatment of Grade III Giant Cell Tumors of the Distal Radius?

PurposeA giant cell tumor (GCT) of bone presenting in the distal radius is rare, however, when they occur, Campanacci Grade III tumors can present formidable reconstructive challenges. They are associated with a high local recurrence rate with intralesional treatment, therefore approaches to reconstruct the wrist after en bloc resection warrant study.QuestionsWe asked: (1) What are the functional outcomes after en bloc resection and reconstruction of the wrist with a unipolar prosthesis in patients with Grade III GCT of the distal radius? (2) What complications occur with use of a unipolar prosthesis in these patients? (3) What are the oncologic outcomes with using en bloc resection and reconstruction with a custom unipolar wrist hemiarthroplasty for Grade III GCTs of the distal radius?MethodsWe retrospectively analyzed 10 patients with Campanacci Grade III GCTs of the distal radius treated by a unipolar prosthesis after wide resection of the tumor between January 2008 and October 2013. During that period, all patients at our medical group who presented with a Grade III GCT of the distal radius were treated with wide resection and reconstruction using a custom unipolar implant. Pre- and postoperative pain at rest were assessed according to a 10-cm VAS score. The functional outcomes of the wrist were assessed using the modified Mayo wrist score, and the degenerative changes were evaluated radiographically by a new rating system based on the Knirk and Jupiter scale. We also analyzed tumor recurrence, metastases, and complications associated with the reconstruction procedure. All patients were available for followup at a mean of 52 months (range, 24–90 months).ResultsAlthough the complication rate associated with prosthetic arthroplasty was relatively high (six of 10), none of our patients experienced severe complications. Two patients reported having occasional pain of the involved wrist at the time of final followup (VAS, preoperative versus postoperative: 0 versus 3; 5 versus 2, respectively). The mean modified Mayo wrist score was 68 (range, 45–90). Degenerative changes were found in three wrists (Grade 1, two patients; Grade 2, one patient). Aseptic loosening occurred in one patient and wrist subluxation occurred in two patients. Lung metastases or local tumor recurrence were not observed.ConclusionsBecause of the proportion of patients who had complications and progressive degeneration with this approach, we recommend first exploring alternatives to reconstruction with custom unipolar wrist hemiarthroplasty after resection of Grade III GCTs of the distal radius, such as fibular autografting. However, this technique provides an alternative for patients with concerns regarding possible morbidity associated with autografting, and for situations when allograft is not available.Level of EvidenceLevel IV, therapeutic study.