Endothelin-1 induces chondrocyte senescence and cartilage damage via endothelin receptor type B in a post-traumatic osteoarthritis mouse model

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羌活汤离子导入联合关节松动术治疗膝骨关节炎寒湿痹阻证临床研究

目的评价羌活汤离子导入联合关节松动术治疗膝骨关节炎(knee osteoarthritis,KOA)寒湿痹阻证的疗效。方法将本院2017年10月-2018年10月符合入选标准的98例KOA患者,按随机数字表法分为2组,每组49例。2组均给予关节松动术治疗,在此基础上,对照组口服硫酸氨基葡萄糖胶囊,观察组经离子导入羌活汤。2组均治疗6周。分别于治疗前后从关节疼痛、关节得温痛减、晨僵、腰身重痛方面行寒湿痹阻证症状评分,采用西安大略和麦克马斯特大学骨关节炎指数(The Osteoarthritis Index at the Universities of Western Ontario and McMaster,WOMAC)评估膝关节功能障碍程度,采用ELISA法检测血清Ⅰ型胶原C端肽(typeⅠcollagen C-terminal peptide,CTX-Ⅰ)、CTX-Ⅱ、抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase isoform 5b,TRACP-5b)及前列腺素E2(prostaglandin E2,PGE2)、P物质(substance P,SP)、多巴胺(dopamine,DA)、5-羟色胺(5-hydroxytryptamine,5-HT)水平,评价临床疗效。结果观察组总有效率为93.9%(46/49)、对照组为77.6%(38/49),2组比较差异有统计学意义(χ^2=4.083,P=0.043)。治疗后,观察组WOMAC指数中关节疼痛、关节僵硬、日常活动受限评分低于对照组(t值分别8.430、9.986、12.776,P<0.01);症状评分中关节疼痛、关节得温痛减、晨僵、腰身重痛评分低于对照组(t值分别为8.825、9.043、7.230、7.034,P<0.01)。治疗后,观察组血清CTX-Ⅰ[(404.99±43.35)μg/L比(458.69±48.61)μg/L,t=21.005]、CTX-Ⅱ[(414.99±43.39)μg/L比(484.06±50.77)μg/L,t=18.991]、TRACP-5b[(2.98±0.35)U/L比(5.67±0.61)U/L,t=9.043]水平均低于对照组(P<0.01);血清PGE2[(167.81±18.79)μg/L比(252.61±27.34)μg/L,t=26.389]、SP[(143.67±15.92)μg/L比(179.55±19.53)μg/L,t=25.416]、DA[(9.15±1.15)μg/L比(13.17±1.81)μg/L,t=10.445]、5-HT[(615.08±63.95)μg/L比(712.69±72.88)μg/L,t=31.004]水平均低于对照组(P<0.01)。结论羌活汤离子导入联合关节松动术可改善KOA患者骨代谢水平,降低疼痛介质分泌,改善临床症状,提高疗效。     

Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Sex differences in the regularity and symmetry of gait in older adults with and without knee osteoarthritis

BackgroundThree-dimensional (3D) motion measured at the lower back during walking can describe the regularity and symmetry of gait that may be related to osteoarthritis (OA) and functional status. However, gait speed and inherent sex differences, regardless of the presence of OA, may confound these measures. Therefore, there is a need to understand the effect of OA separately among males and females, without the confounding influence of gait speed.ObjectiveTo investigate the difference in 3D gait regularity and symmetry measures between gait speed-matched males and females with and without knee OA.MethodGait regularity and symmetry were computed as autocorrelations of pelvic accelerations during treadmill walking in four groups of older adults: healthy asymptomatic females (AsymF; n = 44), healthy asymptomatic males (AsymM; n = 45), females diagnosed with knee OA (OAF; n = 44), and males diagnosed with knee OA (OAM; n = 45). Data were obtained from a larger research database, allowing for the matching of gait speed between groups. The main effect of OA, sex, and interaction effect between them was examined for the 3D gait regularity and symmetry measures at an alpha level of 0.05.ResultsThere was no main effect of OA on any variable, but there was a significant main effect of sex on mediolateral and anteroposterior gait regularity measures. Specifically, females demonstrated significantly greater gait regularity, most notably in the mediolateral directions compared to males.ConclusionOlder adult females were found to display significantly greater mediolateral gait regularity as compared to males, regardless of the presence of OA. Further, this difference exists among matched gait speeds, suggesting it is not the result of gait speed. Overall, these results highlight the importance of sex-specific analyses and considering gait speed when examining gait acceleration patterns near the center of mass for both cross sectional and longitudinal gait assessments.     

Biomechanical analysis during single-leg squat in individuals with knee osteoarthritis

Backgroud: The single-leg squat (SLS) is a functional task to evaluate the abnormal movement patterns and potential neuromuscular deficits in the lower limbs. Still, it is unknown if SLS could provide information to older adults with knee osteoarthritis (KOA). The study’s objective was to analyze the EMG pattern, kinematics, and postural control in individuals with and without KOA during SLS.Methods: Participated in this study, 60 volunteers of both sexes, 30 had KOA (allocated into the KOA group - KOAG), and 30 were healthy (allocated into the Healthy Group - HG) performing the single-leg squat. Surface electromyography (EMG) was assessed for the gastrocnemius medialis (GM), biceps femoris (BF), gluteus medius (GLM), rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), and tibialis anterior (TA) in two phases (downward – P1 and upward – P2). The kinematic data was evaluated using an electrogoniometer. The center of pressure (CoP) was obtained using data collected from a force plate.Results: EMG activity was increased for GM and TA muscles during the P1 of the movement and the GM and GLM muscles during P2 of the movement. The angular displacement of the KOAG was lower when compared with the HG. There was no statistical difference for the co-contraction and postural control data.Conclusions: The SLS analysis showed that EMG activity of the muscles TA, GM, and GLM was increased in the KOAG, but this pattern could be affected by fear of movement leading to reduced knee angular displacement.     

Articular cartilage repair & joint preservation: A review of the current status of biological approach

The articular cartilage of the joint is the thin viscoelastic layer of the connective tissue. It has a unique anatomy and physiology, which makes the repair of the articular cartilage damage more difficult and challenging due to its limited healing capacity. Increasing knowledge regarding the importance of articular cartilage for joint preservation has led to increased attention on early identification of cartilage damage as well as degeneration in order to delay osteoarthritis. There are various treatment modalities ranging from preventive management, physical therapy, pharmacological, non-pharmacological and surgical treatments exist in current literature. However most of the studies have limited long term follow up and mainly consists of small case series and case reports. This is an up to date concise review discussing the available management options for articular cartilage damage starting to lifestyle modification to pharmacotherapy, physiotherapy, and osteobiologics till various joint preservation techniques that have been in use currently.     

Effects of total knee arthroplasty for primary knee osteoarthritis on postural balance: A systematic review

BackgroundKnee osteoarthritis is often related to physical function impairment. Although total knee arthroplasty is considered effective for advanced cases of knee osteoarthritis, its effects on postural balance is a topic of debate.Research questionWhat are the effects of total knee arthroplasty for primary knee osteoarthritis on postural balance compared to preoperative status and/or to healthy controls?.MethodsLongitudinal studies (with more than 1-month follow-up) assessing postural balance measures (either clinical-based such as balance scales or laboratory-based such as postural sway) were considered eligible and selected in a 2-phase process. Six main electronic databases were searched, complemented by 3 grey literature sources. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tools.ResultsA total of 19 studies were included for qualitative synthesis, of which 14 had low and 5 had a moderate risk of bias. The follow-up period ranged from 1–24 months. Most studies (n = 11) presented comparisons to preoperative status only. From these, 7 studies reported relevant improvements in postural balance, 2 reported partial improvements, and 2 no improvements. The remaining studies (n = 8) presented comparisons to healthy controls and, although improvements following total knee arthroplasty were consistently observed, only one study reported postural balance measures comparable to that of controls.ConclusionsThe majority of studies reported relevant improvements (especially in clinical-based measures) compared to preoperative evaluations, although inconsistencies were found possibly due to variability in studies' populations, assessment tools, and follow-up times. Despite this, persistent deficits in postural balance were commonly observed when compared to healthy controls.SignificanceThis evidence synthesis could better inform clinicians and researchers about the therapeutic effects and limitations of total knee arthroplasty concerning postural balance. Standardization of assessment tools is recommended to strengthen the certainty of cumulative evidence.     

关节腔渗透压调控骨关节炎的研究进展

骨关节炎是一种慢性、进行性、不可逆性的关节退行性疾病,是一种中老年人的常见疾病,被认为是全球致残率较高的疾病之一。近年来,随着经济发展和人口老龄化,骨关节炎的患者数量在不断增加,这也让骨关节炎在临床上得到了极大的重视。而临床上治疗骨关节炎的一个关键性问题是关节软骨的丢失和难以自我修复。渗透压可以通过调节细胞体积和调控离子通道影响软骨细胞的生理代谢,从而影响关节软骨的损伤和修复。这一过程可能在骨关节炎发生发展中起到了重要作用。本文就离子通道、渗透压和骨关节炎三者间的相关性作一综述。