Wenhao Zheng

Butein inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and slows the progression of osteoarthritis in mice

Abstract Osteoarthritis (OA) is a progressive degenerative disease characterized by irreversible articular cartilage destruction. Butein, a polyphenolic compound isolated from the stem bark of cashews and Rhus verniciflua Stokes, has been reported to have anti‐inflammatory effects. This study aimed to assess the effect of butein on human OA chondrocytes and mice OA models induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with butein at 10, 50 &mgr;M and subsequently stimulated with IL‐1&bgr; (10 ng/ml) for 24 h. Production of NO, PGE2, TNF‐&agr; and IL‐6 was evaluated by the Griess reaction and ELISAs. The mRNA expression of COX‐2, iNOS, TNF‐&agr;, IL‐6, MMP‐1, MMP‐3, MMP‐13, ADAMTS‐4, ADAMTS‐5, COL‐2 and SOX‐9 were measured by real‐time PCR. The protein expression of COX‐2, iNOS, MMP‐13, COL‐2, SOX‐9, p65 and I&kgr;B‐&agr; were detected by Western blot. P65 nuclear translocation was detected by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that butein significantly inhibited the IL‐1&bgr;‐induced production of NO and PGE2, expression of COX‐2, iNOS, TNF‐&agr;, IL‐6 and MMP‐13, degradation of COL‐2 and SOX‐9 at mRNA and protein levels as well as MMP‐1, MMP‐3, ADAMTS‐4 and ADAMTS‐5 gene expression. Furthermore, butein dramatically suppressed IL‐1&bgr;‐stimulated I&kgr;B‐&agr; degradation and NF‐kB p65 activation. In vivo, the cartilage in butein‐treated mice exhibited less Safranin O loss, cartilage erosion and lower OARSI scores. Butein also reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that butein may be a potential agent in the treatment of OA. Graphical abstract Figure. No Caption available. HighlightsButein inhibited the IL‐1&bgr;‐induced inflammatory mediators in human osteoarthritis chondrocytes.Butein inhibited the IL‐1&bgr;‐induced degradation of type II collagen and SOX‐9 in human osteoarthritis chondrocytes.Butein inhibited the IL‐1&bgr;‐induced I&kgr;B‐&agr; degradation, NF‐kB p65 activation and NF‐&kgr;B p65 nuclear translocation in human osteoarthritis chondrocytes.Butein attenuated the arthritis in mice osteoarthritis models.

Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice

&NA; Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Fisetin, a polyphenol extracted from fruits and vegetables, has been reported to have anti‐inflammatory effects. Our study aimed to investigate the effect of fisetin on OA both in vitro and in vivo. In vitro, chondrocytes were pretreated with fisetin alone or fisetin combined with sirtinol (an inhibitor of SIRT1) for 2 h before IL‐1&bgr; stimulation. Production of NO, PGE2, TNF‐&agr; and IL‐6 were evaluated by the Griess reaction and ELISAs. The mRNA (COX‐2, iNOS, MMP‐3, MMP‐13, ADAMTS‐5, Sox‐9, aggrecan and collagen‐II) and protein expression (COX‐2, iNOS, MMP‐3, MMP‐13, ADAMTS‐5 and SIRT1) were measured by qRT‐PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen‐II and SIRT1. SIRT1 activity was quantified with SIRT1 fluorometric assay kit. The in vivo effect of fisetin was evaluated by gavage in mice OA models induced by destabilization of the medial meniscus (DMM). We found that fisetin inhibited IL‐1&bgr;‐induced expression of NO, PGE2, TNF‐&agr;, IL‐6, COX‐2, iNOS, MMP‐3, MMP‐13, ADAMTS‐5. Besides, fisetin remarkably decreased IL‐1&bgr;‐induced degradation of Sox‐9, aggrecan and collagen‐II. Furthermore, fisetin significantly inhibited IL‐1&bgr;‐induced SIRT1 decrease and inactivation. However, the inhibitory effect of fisetin was obvious abolished by sirtinol, suggesting that fisetin exerts anti‐inflammatory effects through activating SIRT1. In vivo, fisetin‐treated mice exhibited less cartilage destruction and lower OARSI scores. Moreover, fisetin reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that fisetin may be a potential agent in the treatment of OA. Graphical abstract Figure. No caption available. HighlightsFisetin inhibited the IL‐1&bgr;‐induced inflammatory mediators in human osteoarthritis chondrocytes.Fisetin inhibited the IL‐1&bgr;‐induced degradation of Sox‐9, aggrecan and collagen‐II in human osteoarthritis chondrocytes.Fisetin inhibited the IL‐1&bgr;‐induced SIRT1 decrease and inactivation in human osteoarthritis chondrocytes.Sirtinol reversed the the inhibitory effect of fisetin on IL‐1&bgr;‐induced inflammatory response in human osteoarthritis chondrocytes.Fisetin alleviated the progression of osteoarthritis in mice models.

Cryptotanshinone protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.

Abstract Osteoarthritis (OA) is a common degenerative disease characterized by progressive erosion of articular cartilage, subchondral bone sclerosis and synovitis. Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza Bunge, has been shown to have potent anti‐inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of CTS on human OA chondrocytes and mice OA models. Human OA chondrocytes were pretreated with CTS (5, 10 and 20 &mgr;M) for 2 h and subsequently stimulated with IL‐1&bgr; for 24 h. Production of NO, PGE2, IL‐6, TNF‐&agr; was evaluated by the Griess reaction and ELISA. The protein expression of COX‐2, iNOs, MMP‐3, MMP13, COX‐2, ADAMTS‐5, JNK, p‐JNK, ERK, p‐ERK, p38, p‐p38, p‐IKK&agr;/&bgr;, p65, p‐p65, I&kgr;B‐&agr;, and p‐I&kgr;B‐&agr; was tested by Western blot. In vivo, the severity of OA was determined by histological analysis. We found that CTS significantly inhibited the IL‐1&bgr;‐induced production of NO and PGE2; expression of COX‐2, iNOS, MMP‐3, MMP‐13, and ADAMTS‐5. Furthermore, CTS in dramatically suppressed IL‐1&bgr;‐stimulated NF‐&kgr;B and MAPK activation. Immunofluorescence staining demonstrated that CTS could suppress IL‐1&bgr;‐induced phosphorylation of p65 nuclear translocation. In vivo, treatment of CTS prevented the destruction of cartilage and the thickening of subchondral bone in mice OA models. These results indicate that the therapeutic effect of CTS on OA is accomplished through the inhibition of both NF‐&kgr;B and MAPK signaling pathways. Our findings provide the evidence to develop CTS as a potential therapeutic agent f or patients with OA. HighlightsCryptotanshinone inhibited the IL‐1&bgr;‐induced inflammatory mediators in human osteoarthritis chondrocytes.Cryptotanshinone inhibited IL‐1&bgr;‐induced inflammatory response through suppressing NF‐&kgr;B and MAPK activation.Cryptotanshinone alleviated the progression of osteoarthritis in mice models.

Salvianolic acid B inhibits IL-1β-induced inflammatory cytokine production in human osteoarthritis chondrocytes and has a protective effect in a mouse osteoarthritis model

Abstract Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti‐inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100 &mgr;M) for 2 h, then incubated with IL‐1&bgr; (10 ng/mL) for 24 h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX‐2, MMP‐13, ADAMTS‐5 and NF‐&kgr;B‐related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal‐injection of either Sal B (25 mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin‐O‐Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8 weeks following the surgery. Sal B inhibited the over‐production of NO and PGE2, while the elevated expression of INOS, COX‐2, MMP‐13 and ADAMTS‐5 were reversed by Sal B in IL‐1&bgr;‐induced chondrocytes. In addition, IL‐1&bgr; significantly induced phosphorylation of NF‐&kgr;B signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL‐1&bgr;‐induced p65 nuclear translocation. In vivo, the cartilage in Sal B‐treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment. HighlightsSalvianolic acid B inhibits IL‐1&bgr;‐induced inflammatory cytokine production.Salvianolic acid B can suppress activation of NF‐&kgr;B signaling.Salvianolic acid B decreases cartilage degradation in a mouse OA model.Salvianolic acid B may be a potential agent in treating and preventing OA.

Silibinin protects against osteoarthritis through inhibiting the inflammatory response and cartilage matrix degradation in vitro and in vivo

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Silibinin, a polyphenolic flavonoid derived from fruits and seeds of Silybum marianum, has been reported to possess various potent beneficial biological effects, such as antioxidant, anti-cancer, hepatoprotective and anti-inflammatory activities. However, the anti-inflammatory effects of silibinin on OA have not been reported. This study aimed to assess the effects of silibinin on OA both in vitro and in vivo. In this study, we found that silibinin significantly inhibited the nterleukin-1β (IL-1β)-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and IL-6, expression of cyclooxygenase2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5, degradation of aggrecan and collagen-II in human OA chondrocytes. Furthermore, silibinin dramatically suppressed IL-1β-stimulated phosphatidylinositol 3 kinase/ protein kinase B (PI3K/Akt) phosphorylation and nuclear factor-kappa B (NF-kB) activation in human OA chondrocytes. In addition, treatment of silibinin not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. Also, the immunohistochemistry results showed that silibinin significantly decreased the expression of MMP-13 and ADAMTS-5 and increased the expression of collagen-II and aggrecan in mice OA. Taken together, these results suggest that silibinin may be a potential agent in the treatment of OA.

Comparison of the Conventional Surgery and the Surgery Assisted by 3d Printing Technology in the Treatment of Calcaneal Fractures

ABSTRACT Purpose: This study was aimed to compare conventional surgery and surgery assisted by 3D printing technology in the treatment of calcaneal fractures. In addition, we also investigated the effect of 3D printing technology on the communication between doctors and patients. Methods: we enrolled 75 patients with calcaneal fracture from April 2014 to August 2016. They were divided randomly into two groups: 35 cases of 3D printing group, 40 cases of conventional group. The individual models were used to simulate the surgical procedures and carry out the surgery according to plan in 3D printing group. Operation duration, blood loss volume during the surgery, number of intraoperative fluoroscopy and fracture union time were recorded. The radiographic outcomes Böhler angle, Gissane angle, calcaneal width and calcaneal height and final functional outcomes including VAS and AOFAS score as well as the complications were also evaluated. Besides, we made a simple questionnaire to verify the effectiveness of the 3D-printed model for both doctors and patients. Results: The operation duration, blood loss volume and number of intraoperative fluoroscopy for 3D printing group was 71.4 ± 6.8 minutes, 226.1 ± 22.6 ml and 5.6 ± 1.9 times, and for conventional group was 91.3 ± 11.2 minutes, 288.7 ± 34.8 ml and 8.6 ± 2.7 times respectively. There was statistically significant difference between the conventional group and 3D printing group (p < 0.05). Additionally, 3D printing group achieved significantly better radiographic results than conventional group both postoperatively and at the final follow-up (p < 0.05). However, No significant difference was noted in the final functional outcomes between the two groups. As for complications, there was no significant difference between the two groups. Furthermore, the questionnaire showed that both doctors and patients exhibited high scores of overall satisfaction with the use of a 3D printing model. Conclusion: This study suggested the clinical feasibility of 3D printing technology in treatment of calcaneal fractures.

Comparison of three surgical fixation methods for dual-bone forearm fractures in older children: A retrospective cohort study

BACKGROUND The aim of this study was to compare the outcomes of dual ESIN (D-ESIN) fixation, hybrid fixation, and open reduction and dual plate (d-plate) fixation in the treatment of dual-bone forearm fractures in children aged 10-16 years. MATERIALS AND METHODS 137 patients with dual-bone forearm fractures (48 patients in the D-ESIN group, 45 patients in the hybrid group, and 44 patients in the d-plate group) were reviewed. Duration of surgery, length of incision, intraoperative blood loss, intraoperative times of fluoroscopy, and duration of postoperative immobilisation were recorded. Radiographic outcomes, functional outcomes, and complication rate were also recorded. RESULTS Surgeries and incisions were significantly shorter, and less intraoperative blood loss occurred, in the hybrid group than the d-plate group (P < 0.001). The hybrid group was also characterised by less intraoperative fluoroscopy times and shorter duration of postoperative immobilisation compared with the D-ESIN group (P < 0.001). The union rate of the ulna at 3 months postoperatively was higher in the hybrid and d-plate groups than in the D-ESIN group (P = 0.003). The union rate of the radius was similar in all three groups (P = 0.403). No significant difference in the union rate of the radius or ulna was observed among groups at 6 months postoperatively (P = 0.052). The mean union time was notably later in the D-ESIN group than in the hybrid and d-plate groups. However, no significant difference in functional outcome or complication rate was observed among the three groups (P = 0.822 and P = 0.912). CONCLUSION Hybrid fixation was superior in terms of the duration of surgery, intraoperative use of fluoroscopy, intraoperative blood loss, duration of postoperative immobilisation, delayed union of the ulna, and bone union time. Therefore, hybrid fixation is a safe and effective treatment for dual-bone forearm fractures in children aged 10-16 years.

Transforaminal lumbar interbody fusion with cortical bone trajectory screws versus traditional pedicle screws fixation: a study protocol of randomised controlled trial

Introduction Transforaminal lumbar interbody fusion (TLIF) has been widely used in the treatment of lumbar degenerative disc disorders and shows favourable clinical results. Recently, cortical bone trajectory (CBT) has become a new trajectory for screw insertion in the lumbar spine. Several biomechanical studies have demonstrated that the CBT technique achieves screw purchase and strength greater than the traditional method. Currently, the available data on the clinical effectiveness of the two performed surgeries, TLIF with CBT screws (CBT-TLIF) and TLIF with traditional pedicle screws (PS-TLIF), are insufficient. This is the first randomised study to compare CBT-TLIF against traditional PS fixation and will provide recommendations for treating patients with lumbar degenerative disc disorders. Methods and analysis A blinded randomised controlled trial (blinding for the patient and statistician, rather than for the clinician and researcher) will be conducted. A total of 254 participants with lumbar disc degenerative disease who are candidates for TLIF surgery will be randomly allocated to either the CBT-TLIF group or the PS-TLIF group at a ratio of 1:1. The primary clinical outcome measures are the incidence of adjacent cranial facet joint violation, fusion rate and the screw loosening rate. Secondary clinical outcome measures are Visual Analogue Scale (VAS) of back pain, VAS of leg pain, Oswestry Disability Index, operative time, intraoperative blood loss and complications. These parameters will be evaluated on day 3, and then at 1, 3, 6, 12 and 24 months postoperatively. Ethics and dissemination This study has been reviewed and approved by the Institutional Review Board of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (batch: 2017–03). The results will be presented in peer-reviewed journals and an international spine-related meeting after completion of the study. Trial registration number NCT03105167; Pre-results.

With versus without bone grafts for operative treatment of displaced intra-articular calcaneal fractures: A meta-analysis

PURPOSE This meta-analysis aimed to investigate the effectiveness of operative treatment of intra-articular calcaneal fractures with bone grafts versus without bone grafts. METHODS The electronic literature database of Pubmed, Embase, and Cochrane library were searched in April 2018. The data on Böhler angle, Gissane angle, calcaneal width, calcaneal height, AOFAS hindfoot scores and complications (including wound edge necrosis, wound infection, deep infection, hematoma and sural nerve injury) were extracted. The Stata 14.0 software was used for the meta-analysis. RESULTS Nine studies including 6 RCTs and 3 retrospective cohort studies met our inclusion criteria. This meta-analysis showed that there was no significant difference between the two groups regarding the Böhler angle (P = 0.44), Gissane angle (P = 0.06), calcaneal width (P = 0.09) and calcaneal height (P = 0.44) postoperatively and at the last follow-up. However, the bone graft group had significantly higher AOFAS scores than the non-bone graft group (P < 0.05). No significant difference was found between the two groups in complications (P = 0.63). CONCLUSION This meta-analysis suggested that operative treatment of intra-articular calcaneal fractures with bone grafts achieved better AOFAS scores than the non-bone graft group. The two groups had similar results in Böhler angle, Gissane angle, calcaneal width and calcaneal height. No increased risk of postoperative complications was identified. More RCTs are required for further research.

Three-dimensional printing assisted ORIF versus conventional ORIF for tibial plateau fractures: A systematic review and meta-analysis

PURPOSE The objective of this meta-analysis was to assess the influence of three dimensional printing technology on the open reduction and internal fixation (ORIF) of tibial plateau fractures from current randomized controlled trials and prospective comparative studies. METHODS The electronic literature database of Pubmed, Embase, and Cochrane library were searched in January 2018. The data operation time, intraoperative blood loss, follow-up knee function (Rasmussen score, HSS) and complications (including infection, screw loosening, knee stiffness, knee instability, posttraumatic osteoarthritis, VTE) were extracted. Stata 12.0 software was used for our meta-analysis. RESULTS 11 RCTs and 6 prospective comparative studies met our inclusion criteria with 358 tibial plateau fractures patients in the 3D group and 378 patients in the routine ORIF group. The meta-analysis showed that there were significant differences in operation time, intraoperative blood loss and bony union time between the 3D group and conventional group. As for the complications and follow-up function recovery evaluated by the excellent and good rate based on HSS and Rasmussen score, no significant differences were found. CONCLUSION The 3D group showed shorter operation time, less intraoperative blood loss and faster union time for patients with tibial plateau fractures. Therefore, compared with conventional ORIF, ORIF assisted by three-dimensional printing technology should be a more appropriate treatment of tibial plateau fractures. Further large-sample randomized controlled trials are needed in the future to confirm the superiority of three-dimensional printing assisted ORIF.