Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

BACKGROUND: The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs. OBJECTIVE: We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs. METHODS: The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments. RESULTS: CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2). CONCLUSIONS: Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.

N-acetyl-L-cysteine attenuates oxidative stress-induced bone marrow endothelial cells apoptosis by inhibiting BAX/caspase 3 pathway.

Bone marrow endothelial cells (BMECs) play a crucial role in the maintenance of bone homeostasis. The decline in BMECs is associated with abnormal bone development and loss. At present, the mechanism of age-related oxidative stress enhancement in BMEC dysfunction remains unclear. Our experiment explored injury caused by oxidative stress enhancement in BMECs both in vivo and in vitro. The BMECs, indicators of oxidative stress, bone mass, and apoptosis-related proteins were analyzed in different age groups. We also evaluated the ability of N-Acetyl-L-cysteine (NAC) attenuate oxidative stress injury in BMECs. NAC treatment attenuated reactive oxygen species (ROS) overgeneration and apoptosis in BMECs in vitro and alleviated the loss of BMECs and bone mass in vivo. In conclusion, this study could improve our understanding of the mechanism of oxidative stress-induced BMECs injury and whether NAC has therapeutic potential in senile osteoporosis.

PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products.

Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.

Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis.

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.

Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice.

PURPOSE: Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain. METHODS: Osteoporosis was induced in mice by ovariectomy (OVX). Pain-related behaviours were assessed by measuring sensitivity to mechanical, thermal and cold stimulation. The expression of pain-related transcripts, such acid-sensing ion channel 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP), was evaluated. Plasma markers of oxidative stress were also measured. In addition, the effects of the reactive oxygen species scavenger phenyl N-tert-butylnitrone (PBN) on these parameters were assessed. RESULTS: The OVX mice presented hyperalgesia, as demonstrated by decreased paw withdrawal thresholds to mechanical stimulation and withdrawal latencies to thermal and cold stimulation, along with upregulated expression of ASIC3, TRPV1 and CGRP in the dorsal root ganglia, spinal cord and thalamus tissue. OVX elevated the plasma levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). However, the administration of PBN alleviated these effects. CONCLUSION: Our results indicated that oxidative stress contributes to hyperalgesia in OVX mice. Enhanced oxidative stress may be associated with osteoporotic pain. Antioxidant treatment could help alleviate chronic pain in postmenopausal osteoporotic patients.

Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding.

BACKGROUND: Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. METHODS: Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC-MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. RESULTS: Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC-MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. CONCLUSIONS: The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.

Platelet-secreted CCL3 and its receptor CCR5 promote invasive and migratory abilities of anaplastic thyroid carcinoma cells via MMP-1.

Platelet counts have been reported to be closely related to distant metastasis of many malignant tumors. Our previous study showed that elevated peripheral blood platelet counts may be an adverse prognostic factor of anaplastic thyroid carcinoma (ATC) patients, indicating that platelets may promote ATC progression. In the present study, we aimed to identify the role of platelets in ATC cell invasion and migration and to explore the underlying mechanisms. We found that platelets can promote the invasive and migratory of ATC cells, which may be related to the interaction between activated platelet-secreted chemokine (C-C motif) ligand 3 (CCL3) and its receptor CCR5. The interaction was shown to induce the upregulation of matrix metalloproteinase (MMP)-1 via NF-κB pathway. These findings could provide a new idea for the research of targeted platelets to inhibit tumor metastasis.

Surgical outcomes of cervical myelopathy due to ossification of posterior longitudinal ligament: Anterior decompression and fusion versus posterior laminoplasty.

BACKGROUND: The purpose of this study was to compare the surgical outcomes of anterior decompression and fusion (ADF) with that of posterior laminoplasty (LAMP) for cervical myelopathy caused by ossification of posterior longitudinal ligament (OPLL). METHODS: We retrospectively assessed the medical records of patients who underwent surgery for cervical myelopathy owing to OPLL between 2007 and 2016 at our institution. Fifty patients were included in this study, including 17 patients in ADF group and 33 patients in LAMP group. Surgical outcomes were assessed under the Japanese Orthopaedic Association (JOA) score. The radiologic and clinical data were compared between two groups. RESULTS: There was no significant difference in age, follow-up time, operation time, blood loss, length of stay, preoperative JOA score, occupying ratio of OPLL, diameter of spinal canal, preoperative and final follow-up C2-C7 Cobb angles, and the change of C2-C7 Cobb angle before and after operation between ADF and LAMP groups. The final follow-up JOA score and the neurological recovery rate were significantly higher in ADF group than in LAMP group, particularly in patients with segmental-type OPLL. Cerebrospinal fluid leakage is a major complication after ADF, C5 paralysis, and axial pain frequently results from LAMP. CONCLUSION: Compared with LAMP, ADF shows better improvement of neurological function in patients with cervical myelopathy due to OPLL, especially in patients with segmental-type cervical OPLL.

Predictors for Poor Outcomes After Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Study of 241 Patients.

OBJECTIVE: Percutaneous endoscopic lumbar discectomy (PELD) is a popular surgical procedure for the treatment of lumbar disc herniation (LDH). However, a small proportion of patients will have poor surgical outcomes. We sought to identify the predictors for poor outcomes after PELD. METHODS: A total of 241 patients who had undergone PELD were followed up. Their numerical rating scale (NRS) for pain and Oswestry Disability Index scores were analyzed. They were divided by outcome (excellent, good, fair, poor) using the MacNab criteria. Their clinical history, physical examination, imaging, and surgical findings were compared among the groups. Ordinal logistic regression analysis was used to identify independent predictors for poor outcomes. RESULTS: The preoperative mean total NRS for back pain, NRS for leg pain, and Oswestry Disability Index scores were 4.3 ± 2.6, 5.6 ± 2.5, and 52.1% ± 23.0%. At 2 years after PELD, the corresponding scores had decreased to 1.2 ± 1.7, 0.9 ± 1.5, and 8.4% ± 11.2% (P < 0.001). The excellent, good, fair, and poor outcome rates were 44.4%, 31.5%, 17.4%, and 6.6%, respectively. Ordinal logistic regression analysis revealed that 2-level PELD (P = 0.001), a history of lumbar fusion (P = 0.007), and Modic changes (P = 0.011) were independent predictors for poor outcomes. Numbness was an independent predictor for excellent outcomes (P = 0.014). CONCLUSIONS: PELD appears to be an effective surgery for LDH. Two-level PELD, a history of lumbar fusion, and Modic changes at the same level were independent predictors for poor outcomes after PELD. Patients with LDH with numbness were more likely to have excellent outcomes.

The change of cervical sagittal alignment after surgery for adolescent idiopathic scoliosis.

OBJECTIVE: The postoperative change in cervical sagittal alignment has an impact on health-related quality of life in adolescent idiopathic scoliosis (AIS) patients who have undergone deformity correction. However, the effect of deformity correction on sagittal cervical profile is still controversial in the literatures. The objective of this study was to investigate the postoperative change in the cervical sagittal alignment of patients with AIS. PATIENTS AND METHODS: A total of 46 AIS patients treated by posterior instrumentation and fusion with pedicle screw constructs were included in the study. Radiographs were collected preoperatively, immediate postoperatively and at the final follow-up. The C2-C7 Cobb angle and C2-C7 sagittal vertical axis (cSVA) were used to assess the cervical sagittal alignment. Spinopelvic alignment parameters, such as thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA), were also measured. The correlations between the cervical sagittal parameters and spinopelvic parameters were analyzed. RESULTS: The incidence of cervical kyphosis was 67.4% preoperatively but increased to 87% postoperatively and 69.5% at the final follow-up. The C2-C7 Cobb angle significantly increased from pre-operation (-1.5°â€¯±â€¯15°) to post-operation (-5.4°â€¯±â€¯7.3°; P < 0.05) and spontaneously decreased to -2.9°â€¯±â€¯10.5° at the final follow up. The cSVA was 18.1 ±â€¯13 mm preoperatively, 17 ±â€¯12.3 mm after surgery and 18.5 ±â€¯9.5 mm at the last follow-up, but the change was not statistically significant (P > 0.05). TK decreased significantly from pre-operation (17.7°â€¯±â€¯14.4°) to post-operation (14.2°â€¯±â€¯7.6°) and spontaneously improved to 16.9°â€¯±â€¯8.2° at the final follow-up. TK showed a significant correlation with the C2-C7 Cobb angle, but not with cSVA, in the preoperative (r = 0.709, P < 0.01), postoperative (r = 0.472, P < 0.01), and last follow-up measurements(r = 0.505, P < 0.01). Compared with patients with preoperative thoracic hypokyphosis or hyperkyphosis, patients with a normal thoracic spine had more significant postoperative changes in the C2-C7 Cobb angle and TK. CONCLUSIONS: Cervical sagittal alignment after deformity correction is altered in AIS patients. An increase in cervical kyphosis after surgery is correlated with a loss of thoracic kyphosis. The change in the cervical sagittal profile may be a compensatory mechanism in response to an abnormal thoracic sagittal profile.

Advanced oxidation protein products induce pre-osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated protein kinases-mediated intrinsic apoptosis pathway.

Osteoblast apoptosis contributes to age-related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age-related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3-E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen-activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague-Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase-dependent, MAPK-mediated intrinsic apoptosis pathway.

Bafilomycin A1 increases the sensitivity of tongue squamous cell carcinoma cells to cisplatin by inhibiting the lysosomal uptake of platinum ions but not autophagy.

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.

Adjacent segment disease after instrumented fusion for adult lumbar spondylolisthesis: Incidence and risk factors.

OBJECTIVE: A potential long-term complication of lumbar fusion is the development of adjacent segment disease (ASD), which may necessitate second surgery and adversely affect outcomes. The objective of this is to determine the incidence of ASD following instrumented fusion in adult patients with lumbar spondylolisthesis and to identify the risk factors for this complication. PATIENTS AND METHODS: We retrospectively assessed adult patients who had undergone decompression and instrumented fusion for lumbar spondylolisthesis between January 2006 and December 2012. The incidence of ASD was analyzed. Potential risk factors included the patient-related factors, surgery-related factors, and radiographic variables such as sagittal alignment, preexisting disc degeneration and spinal stenosis at the adjacent segment. RESULTS: A total of 154 patients (mean age, 58.4 years) were included. Mean duration of follow-up was 28.6 months. Eighteen patients (11.7%) underwent a reoperation for ASD; 15 patients had reoperation at cranial ASD and 3 at caudal ASD. The simultaneous decompression at adjacent segment (p=0.002) and preexisting spinal stenosis at cranial adjacent segment (p=0.01) were identified as risk factors for ASD. The occurrence of ASD was not affected by patient-related factors, the types, grades and levels of spondylolisthesis, surgical approach, fusion procedures, levels of fusion, number of levels fused, types of bone graft, use of bone morphogenetic proteins, sagittal alignment, preexisting adjacent disc degeneration and preexisting spinal stenosis at caudal adjacent segments. CONCLUSION: Our findings suggest the overall incidence of ASD is 11.7% in adult patients with lumbar spondylolisthesis after decompression and instrumented fusion at a mean follow-up of 28.6 months, the simultaneous decompression at the adjacent segment and preexisting spinal stenosis at cranial adjacent segment are risk factors for ASD.

Advanced oxidation protein products accelerated the bone loss and weakened bone strength in ovariectomised rats.

INTRODUCTION: Advanced oxidation protein products (AOPPs) are prevalent in several kinds of disorders. Previous research revealed that the levels of AOPPs in postmenopausal women were significantly higher than that in premenopausal women. Whether AOPPs have any effect on bone loss remains unclear. Our research analysed the role of AOPPs on the development of osteoporosis in ovariectomised (OVX) rats. METHODS: Female SD rats were divided into five groups (SHAM, OVX+PBS, OVX+RSA (Rat Serum Albumin), OVX+AOPPs, OVX+AOPPs+SOD) and subjected to sham or ovariectomy. PBS, RSA, and AOPPs were injected daily with or without intragastric administration of superoxide dismutase (SOD) after surgery. Every 4 weeks blood and the tibia were harvested from eight rats in each group. The expression of osteocalcin and CTX-I (C-terminal crosslinking telopeptide of type I collagen) in serum was measured by ELISA, and the tibiae were subjected to metaphyseal three-point bending and µCT analysis. RESULTS: AOPPs increased the serum level of osteocalcin and CTX-I. µCT showed AOPPs decreased bone mass at week 4 and week 8, while significant differences in Fmax and energy absorption were found between the PBS and AOPPs groups at week 20 and week 24. No significant differences were found between the AOPPs and AOPPs+SOD groups at any time. CONCLUSIONS: AOPPs accelerated the bone loss and weakened bone strength in OVX rats.

Does cervical disc arthroplasty have lower incidence of dysphagia than anterior cervical discectomy and fusion? A meta-analysis.

OBJECTIVE: Dysphagia is a common occurrence after anterior cervical spine surgery. The aim of this meta-analysis was to evaluate the incidence of dysphagia after ervical disc arthroplasty (CDA) compared with anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS: The electronic databases, including PubMed, EMBASE and Cochrane Central Register of Controlled Trials, were searched to identify the randomized controlled trials comparing CDA with ACDF. Studies were included only if the incidence of postoperative dysphagia was investigated. Study selection, "risk of bias" assessment, and data extraction were independently performed by two investigators. Data analyses were conducted with RevMan 5.3 software. RESULTS: Ten studies involving 2711 patients (CDA group, n=1512; ACDF group, n=1199) were identified. All studies were determined to have a low risk of bias. Pooling analysis of these studies showed that the incidence of dysphagia was 9.46% (143/1512) after CDA versus 12.09% (145/1199) after ACDF. Meta-analysis showed the statistical difference between two groups with regards to the incidence of dysphagia (risk ratio 0.76; 95% confidence interval [0.61, 0.94]; P=0.01). CONCLUSION: This meta-analysis indicates that patients have a significantly lower incidence of dysphagia after CDA than after ACDF. Additional studies are needed.