Preparation of a biphase composite scaffold and its application in tissue engineering for femoral osteochondral defects in rabbits.

PURPOSE: Three-dimensional bioactive scaffolds are useful tools for stem cell implant in tissue-engineering. For chondral and subchondral repair, the chondroinductive and osteoinductive property of a scaffold is a major challenge. The scaffolds that aim to osteogenic differentiation have been well studied. However, cartilage cells can hardly be induced for osteogenesis, and monophase scaffolds cannot ideally repair both cartilage and subchondral defects at the same time. METHODS: We developed a novel biphase composite scaffold and observe its application osteochondral defects. We combined the advantages of silk-fibroin/chitosan (SF/CS) scaffold in chondrogenic differentiation and the silk-fibroin/chitosan/nano-hydroxyapatite (SF/CS/nHA) scaffold in osteogenic differentiation and bone regeneration, and synthesized a SF/CS-SF/CS/nHA scaffold, which contained both the chondrocytic phase (SF/CS) and the osteoblastic phase (SF/CS/nHA). RESULTS: The biphase scaffold exhibited a porosity ratio around 90% and a water absorption ratio about 822%. A similar degradation property to traditional monophase scaffolds was observed. Bone mesenchymal stem cells (BMSCs) showed a good proliferation on this scaffold. Expression of two types of collagen was inducable for BMSCs on the scaffold. Neoformative extracellular matrix integrated with the scaffold was observed by the scanning electron microscope. When implanted in the lesion site in the rabbit femur with cartilage injury, mixing and filling function were exerted by the cell-scaffold constructs (CSCs). Micro-CT scanning revealed both chondral and subchondral layers were repaired. Moreover, type I and II collagens were both expressed in the implanted CSCs. CONCLUSIONS: Chondral and subchondral repair can be achieved using the biphase scaffold implant that permits both chondrogenesis and osteogenesis from BMSCs. This approach has the potential to be clinically used for tissue engineering implantation.

Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF.

Decreased local and systematic matrix Gla protein (MGP) expression and its link to radiographic progression in ankylosing spondylitis patients.

BACKGROUND: Decreased serum levels of uncarboxylated matrix Gla-protein (ucMGP) have been detected in Ankylosing Spondylitis (AS) patients. The current study was to investigate the expression of MGP in AS tissues as well as the relationship between serum ucMGP (an inactive form of MGP) levels and radiographic severity in AS patients. METHODS: Local MGP expression were assessed by Western blot and RT-PCR in hip synovial tissues from patients with AS and control subjects. In addition, the serum level of ucMGP was assessed by enzyme-linked immunosorbent assay in 68 healthy subjects and 62 patients with AS. The radiographic progression of AS was classified according to the radiographic events of modified New York Criteria for sacroiliac joint evaluation and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system for spine assessment. RESULTS: MGP expression was downregulated in AS patients compared to controls in hip tissues. Decreased levels of ucMGP in serum were found in AS patients compared with healthy controls. ucMGP levels in serum of AS patients were significantly negatively correlated with the disease radiographic severity evaluated by modified New York grading criteria (r = -0.293, p = 0.045) and mSASSS system (r = -0.361, p = 0.03). CONCLUSIONS: MGP expression is impaired in patients with AS. A low serum level of ucMGP in the setting of AS is linked to increased structural damage, emphasizing the role of MGP in the suppression of new bone formation.

Lipopolysaccharide preconditioning attenuates apoptotic processes and improves neuropathologic changes after spinal cord injury in rats.

We have shown earlier that administration of low-dose lipopolysaccharide (LPS) significantly contributed to recovery of motor function after traumatic spinal cord injury in the adult female rat. Using the same standardized animal model, we have now designed a set of experiments to test the hypothesis that LPS preconditioning attenuates stress-related apoptotic processes early after spinal cord trauma. The lower thoracic spinal cord injury in adult female Sprague-Dawley rats was caused by a 10 g weight rod drop from 25 mm on the dural surface of the exposed spinal cord at T10. The rats were randomly assigned to three groups: Sham injury, control (received normal saline alone), and LPS preconditioning (0.2 mg/kg, ip; 72 h prior to the injury). The animals were euthanized at 72 h postinjury. Neuropathologic changes were assessed using hematoxylin and eosin staining. SCI-induced apoptosis were observed by transmission electron microscopy. Caspase-3, cleaved caspase-3, Bax, and Bcl-2 were examined with immunohistochemistry or Western blotting. Compared with the control group, LPS preconditioning group showed significant improvement in the SCI-induced morphology changes. Furthermore, LPS preconditioning reduced the expressions of apoptotic markers caspase-3, cleaved caspase-3, and Bax, upregulated the expression of antiapoptotic marker Bcl-2 in the samples of spinal cord. Low-dose LPS attenuated the recruitment of inflammatory cells and the proliferation of glial cells in the site of injury. LPS preconditioning has neuroprotective effects against TSCI in rats due to its antiapoptosis properties as shown by the inhibition of caspase pathway and the upregulation of antiapoptotic protein.

Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia-reperfusion injury in rats is linked with inhibition of cyclin-dependent kinase 5.

BACKGROUND: Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, has been shown to exert a variety of pharmacological effects including neuroprotective properties. However, the mechanism of neuroprotection is not fully understood. This study was designed to explore the mechanism of BYHWD in the treatment of spinal ischemia-reperfusion injury in rats. METHODS: Twenty-eight male Sprague-Dawley rats, weighting 250-280 g, were used, and were randomly divided into four groups with 7 animals in each: sham operation group (Control), spinal ischemia with saline (SI + Saline), spinal ischemia with BYHWD (SI + BYHWD), and spinal ischemia with roscovitine (SI + R). After 60 minutes of spinal ischemia followed by 72 hours of reperfusion, motor function of hind limbs, spinal ischemic infarction volume, the number of apoptotic cells, and cyclin-dependent kinase 5 (Cdk5) were examined. RESULT: Ischemia-reperfusion resulted in injury of the spines, while BYHWD significantly improved spinal function. The spinal infarction volume, number of apoptotic cells, and Cdk5 were decreased by administration of BYHWD. The similar improvements were seen with the pre-treatment of roscovitine. CONCLUSIONS: BYHWD prevented the ischemia-reperfusion-induced spinal injury in rats. The protective function of BYHWD was, in part, linked with inhibition of Cdk5.

Lipopolysaccharide preconditioning attenuates neuroapoptosis and improves functional recovery through activation of Nrf2 in traumatic spinal cord injury rats.

The previous studies suggested that low-dose lipopolysaccharide (LPS) provides neuroprotection against subsequent challenge with ischemic/reperfusion injury in the brain. But there were few reports about the neuroprotective effects of low-dose LPS against spinal cord injury (SCI). In this study, we evaluated the effect of low-dose LPS preconditioning on neuroapoptosis status after traumatic SCI (TSCI), using a standardized contusion model (NYU, New York University, impactor). SCI-induced rats were randomly divided into three groups: sham operation, control (receiving only normal saline) and LPS preconditioning (0.2 mg/kg, ip; 72 hours before injury). Neurologic function was assessed by the Basso, Beattie and Bresnahan (BBB) score at 6, 12, 24, 48 and 72 hours after TSCI. Rats were sacrificed at 72 hours postinjury. Histological changes were studied using Nissl staining. Apoptotic neural cells were assessed using the TdT-mediated dUTP Nick End Labeling (TUNEL) assay. Nuclear factor erythroid 2-related factor 2 (Nrf2) and caspase-3 were detected with immunohistochemistry and Western blot. LPS preconditioning reduced neuron apoptosis, improved neurologic outcome and actived Nrf2 expression. Moreover, Histological changes and the number of apoptotic cells were correlated with Nrf2 expression after the rats suffered the SCI. Our results suggest that LPS preconditioning exerted a neuroprotective effect against TSCI in rats, and activation of Nrf2 was believed to be one of the contributing mechanisms.

The effects of NSAIDs on types I, II, and III collagen metabolism in a rat osteoarthritis model.

The effects of long-term use of celecoxib, ibuprofen, and indomethacin on types I, II, and III collagen metabolism were evaluated in rat osteoarthritis (OA) model. One hundred and thirty wistar rats were randomly divided into 4 groups: the celecoxib group, the ibuprofen group, the indomethacin group, and the normal saline group. The osteoarthritis was induced by the excision of the left Achilles tendon. In the 3rd, 6th, and 9th month of treatment after surgically induced osteoarthritis, the articular cartilage was observed with microscope using HE staining. The expression of proteoglycans was semiquantified using toluidine blue staining. And, the expressions of types I, II, and III collagen in chondrocytes were examined using immunohistochemistry. The results suggested that celecoxib had no remarkable effects on the expression of types I, II, and III collagen. Ibuprofen upgraded the expression of types I, II, and III collagen and increased the synthesis of collagen. Indomethacin suppressed the expression of type II collagen and enhanced the expression of types I and III collagen. Therefore, during the long-term use of NSAIDs in osteoarthritis, celecoxib may have no remarkable influences on collagen metabolism of the articular cartilage and may be the ideal choice in the treatment of chronic destructive joint disease when anti-inflammatory drugs need to be used for a prolonged period. Ibuprofen may be unfavorable, and indomethacin may be harmful to collagen metabolism in OA treatment.

FGF19 protects against obesity-induced bone loss by promoting osteogenic differentiation.

Human fibroblast growth factor 19 (FGF19) has become a potential therapeutic target for metabolic-related diseases. However, the effects of FGF19 on obesity-induced bone loss have not been completely elucidated. The aim of this study was to investigate the protective effects of FGF19 in high-fat diet (HFD)-fed obese mice and palmitic acid (PA)-treated osteoblasts and to further explore its underlying mechanisms. In vivo, we found that FGF19 alleviated the decreased bone mineral density (BMD) induced by HFD. Micro-CT analysis of femur samples and histological analysis indicated that FGF19 alleviated HFD-induced loss of bone trabeculae and damage to the bone trabecular structure. In vitro, the results suggested that FGF19 ameliorated the PA-induced decline in osteoblast proliferation, increased cell death and impaired cell morphology. Additionally, FGF19 protected against the decline in activation of alkaline phosphatase (ALP) and protein expression of Collagen-1, Runx-2, and osteopontin (OPN) induced by PA. Furthermore, FGF19 might enhance osteogenic differentiation via the Wnt/ß-catenin pathway and inhibit osteoclastogenesis by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis, thus attenuating the negative effect of PA in osteoblasts. In conclusion, our results suggested that FGF19 might promote osteogenic differentiation partially through activation of the Wnt/ß-catenin pathway and alleviate obesity-induced bone loss.

Clinical profile of musculoskeletal injuries associated with the 2008 Wenchuan earthquake in China.

BACKGROUND: The Wenchuan earthquake was an enormous devastating disaster and caused mass casualties. The descriptive analysis presented here serves as a reference not only for present injury intervention but also for future earthquake disaster response. METHODS: A total of 205 patients with a musculoskeletal injury were admitted in two teaching hospitals. We conducted a retrospective review of medical records to document the injury profile, chief complaints, damage locations and types, subsequent treatment, and prognosis. RESULTS: Of the 205 patients, fracture was the major type of injury (78.0%). Forty patients were determined to have crush injuries and 19 patients had crush syndromes. Open fractures, multiple fractures and comminuted fractures were common. Fracture-associated neural injuries and trauma-associated infections were also common. Surgical treatments included debridement, bone traction, external fixation, open reduction and internal fixation, and spinal fixation. All the patients were effectively treated with few complications, a low deformity rate and no death. CONCLUSION: For emergency conditions after a major earthquake, pre-hospital emergency care is highly important. After the patients are transported to the hospital, we should plan individualized treatment according to the patients' respective clinical features, and at the same time, prevent and cure the related complications in a timely manner in order to reduce mortality and disability rates.

Comparison of three different bone graft methods for single segment lumbar tuberculosis: A retrospective single-center cohort study.

OBJECTIVE: To compare the clinical efficacy of one stage posterior debridement with iliac bone graft, titanium mesh bone graft or granular bone graft in the surgical treatment of single segment lumbar tuberculosis. METHODS: Ninety-eight patients who underwent one stage posterior debridement, bone graft and internal fixation for single segment lumbar tuberculosis from 2015 to 2018 were involved in this study, involving 32 case in iliac bone graft group, 32 case in titanium mesh bone graft group and 34 cases in granular bone graft group. The primary outcomes involved operative time, operative blood loss, postoperative hospital stay, visual analogue scale (VAS) score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), ASIA grade and postoperative complications. The secondary outcomes were Cobb angle correction and loss, and bone graft fusion time. All the outcomes were recorded and analyzed. RESULTS: Compared with iliac bone graft and titanium mesh bone graft group, granular bone graft had shorter operative time (P = 0.003), less operative blood loss (P = 0.010) and shorter bone graft fusion time (P < 0.001). With the follow-up of 14-36 months, the VAS score, ESR, CRP and neurological function in the three groups were all significantly improved (P < 0.05). The bone graft fusion time of the granular bone graft group was significantly shorter than iliac bone graft group and titanium mesh bone graft (P < 0.05), but no significant differences were found in the correction and loss of Cobb angle, and the incidence of complications among the three groups (n.s.). CONCLUSION: Granular bone graft has less surgical trauma and shorter bone graft fusion time compared with iliac bone graft and titanium mesh bone graft in the surgical treatment of single segment lumbar tuberculosis. The three methods may achieve comparable clinical efficacy in alleviating symptoms, correcting kyphosis and improving neurological function for appropriate cases.

Implant complications after one-level or two-level cervical disc arthroplasty: A retrospective single-centre study of 105 patients.

The aim of study was to investigate the complications of cervical disc arthroplasty (CDA) and to discuss the factors affecting the mobility of the prosthesis and the measures to prevent these complications. Hundred and five patients who underwent CDA between 2009 and 2016 were enrolled. The clinical and radiographic outcomes were used to assess and the complications were recorded as well.All the patients were followed-up with an average of 41.30 ±â€Š16.90 months with an average age of 47.90 ±â€Š9.22 years. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores improved significantly at the final follow-up (FU) compared with the preoperative values. At the final FU, the overall incidence of heterotopic ossification (HO) was 51.42%. The distribution of different grades of HO was low-level HO (53.7%) and high-level HO (46.3%). No significant differences were found in the NDI, VAS, or JOA scores between patients with HO and those without HO (P > .05). In the high-level HO patients, the range of mobility (ROM) was significantly reduced compared with the low-level HO patients and those without HO (P < .05). The anterior displacement, subsidence, and instability were observed in 1 patient respectively and the segmental kyphosis, adjacent segment degeneration in 3 patients respectively. The patient of CDA instability also suffered severe neck pain and the revision surgery was performed.Postoperative complications in CDA such as HO, segmental kyphosis, and prosthesis displacement are prone to occur, affecting prosthesis mobility. Surgical indications should be strictly controlled, and intraoperative and postoperative treatments should be given great attention in order to reduce prosthesis-related complications.

Oblique lateral interbody fusion combined percutaneous pedicle screw fixation in the surgical treatment of single-segment lumbar tuberculosis: A single-center retrospective comparative study.

OBJECTIVE: To evaluate the clinical efficacy of oblique lateral interbody fusion combined posterior percutaneous pedicle screw fixation in the treatment of single segment lumbar tuberculosis. METHODS: Patients who underwent surgical treatment for single segment lumbar tuberculosis from 2015 to 2018 in our department were retrospectively included in this study. The included patients were divided into two groups, namely oblique lateral interbody fusion combined percutaneous pedicle screw fixation (OLIF) group and traditional posterior transforaminal or transpedicular approach debridement and pedicle screws fixation (PTA) group, according to the surgical methods. Outcomes including operative time, operative blood loss, hospital stay, visual analogue scale (VAS) score, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Cobb angle correction and loss, bone fusion time, ASIA grade and complications were all recorded and compared. RESULTS: A total of 60 patients were included in this study, involving 23 patients in the OLIF group and 37 patients in the PTA group. The OLIF group had less operative time, blood loss and shorter hospital stay compared with the PTA group (P < 0.05). Both the two groups achieved significant improvements in ESR, CRP and ASIA grade at the last follow-up (P < 0.05), but no significant differences were found between them (P>0.05). There were no significant differences in Cobb angle correction and loss between the two groups (P > 0.05), but the bone graft fusion time of the OLIF group was significantly shorter than the PTA group (P < 0.05). The two groups achieved similar improvement in VAS score and ODI at 12 months postoperative and the last follow-up, however, OLIF group had a lower VAS score and ODI at 1 month, 3 months and 6 months postoperative (P < 0.05). No significant difference was found in complications between the two groups (P > 0.05) and all patients were cured after active treatment. CONCLUSIONS: Both OLIF and PTA can achieve satisfactory clinical efficacy in the surgical treatment of single segment lumbar TB, but OLIF has the advantages of less surgical trauma, faster postoperative recovery and shorter bone fusion time.

Combined Application of Dexamethasone and Tranexamic Acid to Reduce the Postoperative Inflammatory Response and Improve Functional Outcomes in Total Hip Arthroplasty.

OBJECTIVE: To evaluate the efficacy and safety of combined use of tranexamic acid (TXA) and dexamethasone (DEX) for anti-inflammatory and clinical outcomes after total hip arthroplasty (THA). METHODS: A total of 100 patients were included in this randomized, controlled study. Patients in the TXA + DEX group were administered TXA at a dose of 15 mg/kg, which was repeated 3 h after THA, and received 20 mg DEX. In contrast, patients in the TXA group were administered TXA at a dose of 15 mg/kg, which was repeated at 3 h postoperatively. C-reactive protein (CRP), interleukin-6 (IL-6) and pain levels, incidence of postoperative nausea and vomiting (PONV), total blood loss and transfusion rates, postoperative fatigue, range of motion (ROM), length of hospital stay (LOS), analgesic rescue and antiemetic rescue consumption, and complications were compared in both groups. RESULTS: The CRP and IL-6 levels were lower in the TXA + DEX group than in the TXA group (all P < 0.001) at 24 h, 48 h, and 72 h postoperatively. Patients in the TXA + DEX group had lower pain scores at rest and walking at 24 h postoperatively (all P < 0.001). In the TXA + DEX group, the incidence of PONV was lower (P = 0.005), postoperative fatigue (P < 0.001) was reduced, and analgesia and antiemetic rescue consumption were also reduced. The total blood loss, transfusion rate, LOS and hip ROM were similar in the two groups. There was no thrombosis, infection, or gastrointestinal bleeding in either group. CONCLUSION: Compared to TXA alone, the combination of TXA + DEX can reduce postoperative inflammatory response, relieve pain, and reduce PONV and fatigue, without increasing the risk of complications. Therefore, the present study suggested that the combination of TXA + DEX is an effective and safe accelerated rehabilitation strategy for patients receiving primary unilateral THA.

Deproteinized bone with VEGF gene transfer to facilitate the repair of early avascular necrosis of femoral head of rabbit.

OBJECTIVE: To explore a new method for early avascular necrosis of femoral head (AVNFH) therapy. METHODS: Sixty-nine AVNFH New Zealand adult rabbits were randomly divided into three groups with equal number. In Group A, deproteinized bone (DPB) that absorbed with recombinant plasmid pcDNA3.1-hVEGF165 was implanted into the drilled tunnel of necrotic femoral head. In Group B, only DPB was implanted. In Group C, only tunnel was drilled without DPB or plasmid implanted. Femoral head specimens were obtained at postoperative 1, 2, 4, 8, 16 weeks. The expression of VEGF165 and collagen I was detected by immunohistochemistry. Bone formation was detected generally by X-ray. Angiogenesis and the repair of the femoral head were observed histologically. RESULTS: The expression of VEGF 165 could be detected 2 weeks after implantation in Group A, but it was not observed in other groups. The result of collagen I expression had a significantly difference 2, 4 and 8 weeks after operation in Group A from those in other groups (P < 0.01). X-ray results indicated that there was more bone formation in Group A than in other groups. The regenerated capillary vessels staining result of necrotic femoral head in Group A was significantly different from those in other groups at postoperative 2 and 4 weeks (P < 0.01). CONCLUSIONS: Transfection of hVEGF165 gene enhances local angiogenesis and DPB-VEGF compound improves the repair of necrotic femoral head. Deproteinized bone grafting with VEGF gene transfer provides a potential method for the treatment of osteonecrosis.

Adenovirus vector­mediated in vivo gene transfer of nuclear factor erythroid­2p45­related factor 2 promotes functional recovery following spinal cord contusion.

The aim of the present study was to investigate whether nuclear factor erythroid 2p45­related factor 2 (Nrf2) overexpression by gene transfer may protect neurons/glial cells and the association between neurons/glial cells and axons in spinal cord injury (SCI). In the present study, Nrf2 recombinant adenovirus (Ad) vectors were constructed. The protein levels of Nrf2 in the nucleus and of the Nrf2­regulated gene products heme oxygenase­1 (HO­1) and NAD (P)H­quinone oxidoreductase­1 (NQO1), were detected using western blot analysis in PC12 cells following 48 h of transfection. Furthermore, the expression of Nrf2 was localized using an immunofluorescence experiment, and the expression of Nrf2, HO­1 and NQO1 were detected using an immunohistochemical experiment in the grey matter of spinal cord in rats. Post­injury motor behavior was assessed via the Basso, Beattie and Bresnahan (BBB) locomotor scale method. In PC12 cells, subsequent to Ad­Nrf2 transfection, nuclear Nrf2, HO­1 and NQO1 levels were significantly increased compared with the control (P<0.01). There was statistically significant changes in the PC12­Ad­Nrf2 group [Nrf2 (1.146±0.095), HO­1 (1.816±0.095) and NQO1 (1.421±0.138)] compared with the PC12­control group [Nrf2 (0.717±0.055), HO­1 (1.264±0.081) and NQO1 (0.921±0.088)] and PC12­Ad­green fluorescent protein group [Nrf2 (0.714±0.111), HO­1 (1.238±0.053) and NQO1 (0.987±0.045); P<0.01]. The BBB scores of the rats indicated that they had improved functional recovery following the local injection of Ad­Nrf2. On the third day following the operation, BBB scores in the adenovirus groups (0.167±0.408) were significantly decreased compared with the SCI group (1±0.894; P<0.05). In the injured section of the spinal cord in the rats, the number of positive cells expressing Nrf2, HO­1 and NQO1 were raised compared with the control and SCI groups, indicating that the adenovirus vector­mediated gene transfer of Nrf2 promotes functional recovery following spinal cord contusion in rats.

One-stage posterior debridement with transverse process strut as bone graft in the surgical treatment of single-segment thoracic tuberculosis: A retrospective single-center study.

This retrospective study investigated the effect of the novel bone graft transverse process strut (TPS) in single segmental thoracic spinal tuberculosis (TB) with the one-stage posterior approach of debridement, fusion, and internal instrumentation. Thirty patients treated in our department from March 2014 to October 2016 were retrospectively analyzed. Surgical time, blood loss, hospitalization time, drainage volume, and follow-up (FU) duration were recorded. The visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, segmental angle, and bone fusion were compared between preoperative and final FU. All the patients were followed for a mean 50.10 ±â€Š25.10 months; the mean age, surgical time in minutes, blood loss, hospitalization time, and drainage volume were 46.23 ±â€Š17.20 years, 195.08 ±â€Š24.0 minutes, 280.77 ±â€Š189.90 mL, 17.31 ±â€Š4.23 days, 436.92 ±â€Š193.81 mL, respectively. VAS and ODI scores were significantly improved at the final FU. The ESR and CRP returned to normal. All patients achieved bony fusion with a mean time of 5.85 ±â€Š1.82 months and a mean segmental angle of 18.77 ±â€Š2.49° preoperatively, which significantly decreased to 9.31 ±â€Š1.54° at the final FU (P < .05). No complications, such as bone graft failure, pleural effusion, fistula, or wound infection were recorded except for cerebrospinal fluid leakage (one case), water electrolyte imbalance (5 cases), superficial infection (1 case), and mild intestinal obstruction (1 case). TPS as a bone graft is reliable, safe, and effective for segmental stability reconstruction for surgical management of single-segment thoracic spinal TB.

High expression of ID1 facilitates metastasis in human osteosarcoma by regulating the sensitivity of anoikis via PI3K/AKT depended suppression of the intrinsic apoptotic signaling pathway.

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma.

TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.

BACKGROUND: Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. METHODS: We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. RESULTS: We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. CONCLUSIONS: Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis.

Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid­induced femoral head necrosis. Vitamin E demonstrates anti­apoptotic and anti­oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid­induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E­treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase­3 and B­cell lymphoma 2 (Bcl­2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl­2­positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase­3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase­3 expression and upregulating Bcl­2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid­induced femoral head necrosis in rabbit models.