Haobo Wu

Sophocarpine attenuates wear particle-induced implant loosening by inhibiting osteoclastogenesis and bone resorption via suppression of the NF-κB signaling pathway in a rat model

Aseptic prosthesis loosening, caused by wear particles, is one of the most common causes of arthroplasty failure. Extensive and over‐activated osteoclast formation and physiological functioning are regarded as the mechanism of prosthesis loosening. Therapeutic modalities based on inhibiting osteoclast formation and bone resorption have been confirmed to be an effective way of preventing aseptic prosthesis loosening. In this study, we have investigated the effects of sophocarpine (SPC, derived from Sophora flavescens) on preventing implant loosening and further explored the underlying mechanisms.

Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata) exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist) and/or SC79 (an AKT agonist) in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

Cross Pin Versus Interference Screw for Femoral Graft Fixation in Hamstring Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Clinical Outcomes

PURPOSEnTo compare the effectiveness of a cross pin and interference screw for femoral graft fixation in primary anterior cruciate ligament reconstruction (ACLR) and provide an appropriate reference for orthopaedic surgeons.nnnMETHODSnThe Medline, Cochrane Library, Web of Science, Scopus, and PubMed databases were searched in March 2016, and comparative trials using cross-pin and interference screw devices for femoral graft fixation in primary hamstring ACLR with clinical outcome measurements were included in the review. Trials with no controlled groups, hybrid fixation, no clinical outcomes, or follow-up of less than 1xa0year were excluded. The quality of the included studies was assessed with the Cochrane Back Review Group 12-item scale. Abstracted data were pooled with fixed or random effects depending on thexa0detected heterogeneity. The outcome measures were the scoring system and physical examination findings, including the Lysholm score, International Knee Documentation Committee score or grade, Tegner score, negative Lachman test, negative pivot-shift test, and instrumented side-to-side anterior-posterior laxity difference.nnnRESULTSnAll the studies reviewed were of prospective design. Within the cross-pin group, patients who underwent hamstring ACLR showed a significantly smaller instrumented side-to-side anterior-posterior laxity difference when compared with interference screw fixation (weighted mean difference, 0.38xa0mm [95% confidence interval, 0.08-0.67xa0mm]; Pxa0= .01), whereas the results of a negative Lachman test and negative pivot-shift test were comparable. Outcomes regarding the scoring system did not reach a significant difference between the 2 groups.nnnCONCLUSIONSnThe statistically decreased instrumented side-to-side anterior-posterior laxity difference achieved by cross-pin transfixation appears to be of limited clinical significance when compared with interference screw fixation in primary hamstring ACLR. Clinically, the performance of cross-pin devices did not show a significant advantage over that of the interference screw for femoral graft fixation in hamstring ACLR.nnnLEVEL OF EVIDENCEnLevel II.

Effect of bisphosphonates on periprosthetic bone loss after total knee arthroplasty: a meta-analysis of randomized controlled trials

BackgroundAseptic loosening and osteolysis are the most common indications after TKA for revision surgery. This meta-analysis which included high-quality randomized controlled trials (RCTs) aimed to analyze the effect of bisphosphonates (BPs) on maintaining periprosthetic bone mineral density (BMD) after total knee arthroplasty.MethodsPubMed, AMED, EMBASE, the Cochrane library, ISI Web of Science, and China National Knowledge Infrastructure were systematically searched, five RCTs were included and the total number of participants was 188. The weighted mean differences with 95% confidence interval were calculated to evaluate the efficacy of BPs on total BMD of knee and the BMD of different periprosthetic regions. A descriptive review was performed for BP-related adverse effects.ResultsThe BPs group presented significantly higher total BMD in proximal part of the tibia than the control group at 3 and 6xa0months (Pu2009<u20090.05), but no significant difference at 12xa0months (Pu2009=u20090.09). The BPs group presented significantly higher BMD in the distal aspect of the femur than that in the control group at 3, 6, 12xa0months. The BPs group presented significantly higher periprosthetic BMD than that in the control group at 3, 6 and 12xa0months in tibial medial and lateral metaphyseal region, and femoral anterior, central and posterior metaphyseal region (pu2009<u20090.05), but no significant difference for tibial diaphyseal region at 3, 6, and 12xa0months. None of the included studies described severe or fatal adverse effects related to BPs.ConclusionBPs have a short-term effect on reducing periprosthetic bone loss after total knee arthroplasty. Compared with diaphyseal region, BPs are more effective on the preservation of BMD in medial lateral metaphyseal regions of proximal tibia and in anterior, central, and posterior metaphyseal region of distal femur.

Cementless Porous Tantalum Monoblock Tibia vs Cemented Modular Tibia in Primary Total Knee Arthroplasty: A Meta-Analysis.

BACKGROUNDnWith the introduction of new fixation systems and designs, there has been a recent reemergence of interest in cementless fixation of the tibial component in total knee arthroplasty. However, little is known regarding the clinical features and survivorship of the cementless porous tantalum monoblock tibial component compared to the conventional cemented modular tibial component.nnnMETHODSnWe conducted a literature search of multiple databases for comparative studies published before June 2015 that investigated the outcomes of cementless porous tantalum monoblock tibia vs conventional cemented modular tibia. A pooled analysis was performed. The outcomes of interest were postoperative functional score, range of motion, Western Ontario and McMaster University Osteoarthritis Index, total complications, reoperation, radiolucent lines, loosening of the tibial component, and length of operation.nnnRESULTSnSix studies involving 977 patients were eligible for the meta-analysis. The use of a cementless porous tantalum monoblock tibial component may associate with a slightly higher functional score, fewer radiolucent lines, and shorter operation. No significant difference was seen in regard to the range of motion, Western Ontario and McMaster University Osteoarthritis Index, total complications, reoperation, and loosening of the component between the 2 groups.nnnCONCLUSIONnHowever, due to variation among the included studies, the use of cementless porous tantalum monoblock tibia seems to achieve no substantial superiority over that of the conventional cemented modular tibia at 5-year follow-up. Data concerning the long-term prognosis of this novel implant should continue to be collected and analyzed.

Effect of a 12-hour natural drainage technique on decreasing blood loss after total knee arthroplasty: a case-control study

Background Different methods of drainage have been used in patients with osteoarthritis after total knee arthroplasty (TKA), but the ideal strategy is controversial. This retrospective case-control study reported a technique of 12-hour natural drainage and aimed to confirm its efficacy and safety in the treatment for blood loss following TKA. Methods There were 231 patients divided into three groups who underwent TKA from January 2014 to July 2017: 76 patients underwent 12-hour natural drainage in Group A, 80 patients underwent 4-hour clamping drainage in Group B, and 75 patients underwent continuous drainage in Group C. All perioperative clinical data were reviewed for statistical analysis. Results The drainage volume and total blood loss after TKA were significantly lower in Group A than that in the other two groups (P<0.05), and serum level of hemoglobin was significantly higher in Group A than that in the other two groups (P<0.05). The maximum of active motion of the knee was greater in Group C at 2 days (P<0.05). Significantly more patients in Group C required blood transfusions (P<0.05). No difference was found in the complication rate among the three groups. Conclusion The 12-hour natural drainage is an effective technique for reducing blood loss for patients following TKA. Compared with temporary clamping drainage and continuous negative pressure drainage, 12-hour natural drainage decreases blood loss, reduces post-operative transfusion requirements, and does not increase the risk of complications. Therefore, this technique of 12-hour natural drainage is recommended to be used in patients after TKA.

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases.

Specnuezhenide Decreases Interleukin-1β-Induced Inflammation in Rat Chondrocytes and Reduces Joint Destruction in Osteoarthritic Rats

As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA.

Artemether attenuates LPS-induced inflammatory bone loss by inhibiting osteoclastogenesis and bone resorption via suppression of MAPK signaling pathway

Osteolysis is an osteolytic lesion featured by enhanced osteoclast formation and potent bone erosion. Lacking of effective regimen for treatment of the pathological process highlights the importance of identifying agents that can suppress the differentiation and function of osteoclast. Artemether is a natural compound derived from Artemisia annua L. and it is popularized for the treatment of malaria. In present study, we demonstrated that artemether could suppress RANKL-induced osteoclastogenesis and expression of osteoclast marker genes such as tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T-cell cytoplasmic 1, and dendritic cell-specific transmembrane protein. It inhibited the osteoclastic bone resorption in a dose-dependent manner in vitro. Furthermore, artemether attenuated RANKL-induced MAPKs (ERK, JNK, p-38) activity. In addition, we have showed that artemether was able to mitigate bone erosion in axa0murine model of LPS-induced inflammatory bone loss. Taken together, these findings suggest that artemether reduces inflammatory bone loss via inhibition of MAPKs activation during osteoclast differentiation, and it might be a potential candidate for the treatment of osteoclast-related disorders.

Y-reconstruction could be better for ACL reconstruction in knee hyperextension versus double-bundle double-tunnel technique: a retrospective comparative study of 56 patients

PurposeTo compare the clinical outcomes of double-bundle (DB) single-tibial tunnel technique and double-tunnel technique for ACL reconstruction in patients with knee hyperextension.MethodsDefined as having constitutional hyperextension of greater than 10°, 56 patients with knee hyperextension who underwent ACL reconstruction were included in this study. To exclude concomitant lesions, preoperative magnetic resonance imaging (MRI) was performed in all knees. 24 patients (Group A) were treated with the anatomic DB/single-tibial tunnel ACL reconstruction and 32 patients (Group B) were treated with DB/double-tibial tunnel ACL reconstruction, all the included patients had knee hyperextension. Clinical results were evaluated by the extension angle, ROM, IKDC 2000 subjective score, rotational stability, pivot-shift test and anterior–posterior translation test before the operation and at the end of follow-up. MRI scan of the knee positioned in full extension was performed after 6 months post-operation. Location of tibial tunnels and graft signal intensity were assessed according to the MRI.ResultsPostoperative extension deficit was detected in Group B, ROM of the injured knee in Group A was from extension angle 8.91u2009±u20093.16° to flexion angle 115.58u2009±u200910.53°. ROM of the injured knee in Group B was from extension angle −u20092.13u2009±u20095.88° to flexion angle 119.25u2009±u200912.63°. Flexion angles of two groups did not show any significant difference (pu2009=u20090.24), while extension angles were quite different (pu2009<u20090.0001). Group A was slightly higher than Group B in IKDC subjective scores, but without significant difference (Group A 45.1u2009±u20096.5, Group B 42.4u2009±u20094.8, pu2009=u20090.09). There was no significant difference between two groups in pivot-shift test. Post-operational MRI showed more anterior located tibial tunnel and higher graft signal intensity in Group B when compared with Group A. One patient in the Group B had ligament retear, and required revision surgery.ConclusionDB/single-tibial tunnel technique restored the knee stability and overcame the shortcomings (such as knee extension deficit and graft impingement) of DB/double tibial tunnel, which might be more suitable for ACL reconstruction in knees with hyperextension.Level of evidenceLevel II to III.