VIP and CRF reduce ADAMTS expression and function in osteoarthritis synovial fibroblasts

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family is known to play an important role in the pathogenesis of osteoarthritis (OA), working on aggrecan degradation or altering the integrity of extracellular matrix (ECM). Thus, the main purpose of our study was to define the role of vasoactive intestinal peptide (VIP) and corticotrophin‐releasing factor (CRF), as immunoregulatory neuropeptides, on ADAMTS production in synovial fibroblasts (SF) from OA patients and healthy donors (HD). OA‐ and HD‐SF were stimulated with pro‐inflammatory mediators and treated with VIP or CRF. Both neuropeptides decreased ADAMTS‐4, ‐5, ‐7 and ‐12 expressions, aggrecanase activity, glycosaminoglycans (GAG), and cartilage oligomeric matrix protein (COMP) degradation after stimulation with fibronectin fragments (Fn‐fs) in OA‐SF. After stimulation with interleukin‐1β, VIP reduced ADAMTS‐4 and ‐5, and both neuropeptides decreased ADAMTS‐7 production and COMP degradation. Moreover, VIP and CRF reduced Runx2 and β‐catenin activation in OA‐SF. Our data suggest that the role of VIP and CRF on ADAMTS expression and cartilage degradation could be related to the OA pathology since scarce effects were produced in HD‐SF. In addition, their effects might be greater when a degradation loop has been established, given that they were higher after stimulation with Fn‐fs. Our results point to novel OA therapies based on the use of neuropeptides, since VIP and CRF are able to stop the first critical step, the loss of cartilage aggrecan and the ECM destabilization during joint degradation.     

关节镜下多种移植物联合重建膝关节前、后交叉韧带

目的:评估关节镜下膝关节前交叉韧带(ACL)与后交叉韧带(PCL)同时重建的技术和临床效果。方法:自2003年6月～2009年10月,27例病人(28膝)经MRI检查及关节镜检查证实ACL和PCL均断裂,其中9膝伴内侧副韧带损伤(MCL),8膝伴后外侧角损伤(PLC),5膝伴内侧半月板破裂,4膝伴外侧半月板损伤。27例患者于伤后3～10周在关节镜下行膝关节前、后交叉韧带联合重建。结果:本组术后早期均未发生严重并发症。术后随访12～88个月,平均(42.67±3.34)个月,Lysholm膝关节功能评分为78～93分,平均(86.67±5.21)分。国际膝关节文件编制委员会(IKDC)综合评定由术前显著异常(D级)28膝,改进为随访时正常(A级)9膝、接近正常(B级)16膝、异常(C级)3膝。结论:关节镜下膝关节前交叉韧带(ACL)与后交叉韧带(PCL)同时重建创伤小、手术操作精细,术后膝关节功能恢复满意。     

A Simple Method for Measuring the Changeable Mechanical Action of Unloader Knee Braces for Osteoarthritis

Purpose

Today's orthotics should be designed to apply the external orthosis moment to the knee joint solely during the stance phase instead of the entire gait cycle. The aim of this study was to validate the reliability of a simple device for measuring forces at the leg–orthosis interface and describe the behavior of an innovating dynamic unloader knee brace built to interrupt its mechanical action during large knee flexion (swing phase of gait).

基于近红外光出射分布特性的膝骨性关节炎病程检测

膝骨性关节炎是中老年人群中常见的慢性、不可逆关节疾病。为了解决常规的CT扫描、核磁共振成像等检测手段存在的辐射影响较大,无法作为常规体检项目,以及无法检测出早期膝关节内部组织病变等缺点,本文提出了一种基于近红外光的无损、快速病程检测手段,结合临床膝关节CT图片用蒙特卡洛方法模拟红外光子在关节内部的运动轨迹,通过高斯函数分析和拟合不同病程下的出射光子分布特征,以有效光子出射率和拟合函数对称轴位置作为指标判定患者病情。该方法的优点在于,对人体不造成任何辐射损害,且能够通过计算机数据分析快速给出判定结果,可作为常规体检项目,便于发现早期病症并及时治疗。仿真实验结果表明该方法的准确率达到92%以上,在膝骨性关节炎的临床检测应用上具有较大的应用价值。     

Association of IL-17A and IL-17F single nucleotide polymorphisms with susceptibility to osteoarthritis in a Korean population

The damage incurred in osteoarthritis (OA) is mediated by a variety of cytokines, growth factors and inflammatory mediators. The importance of the interleukin-17 (IL-17) family in inflammatory and autoimmune disease is becoming increasingly apparent. Microsatellite association mapping reveals a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13. IL-17A and IL-17F genes that resided on chromosome 6p12.3-q13 are believed to play an important role in the primary OA susceptibility. We investigated the allele and genotype of IL-17A G-197A and IL-17F T7488C in 302 OA patients and 300 healthy subjects as controls. We employed a PCR-SSCP assay to identify the genotypes IL-17A G-197A and IL-17F T7488C. For IL-17A G-197A, there were significant differences in frequencies of genotype and allele of IL-17A G-197A between OA patients and controls (both p < 0.0001). For IL-17F T7488C, there were no significant differences in the allele frequency and genotype distribution for IL-17F T7488C between OA patients and controls (p = 0.938 and p = 0.1735, respectively). In conclusion, current study showed that polymorphism of IL-17A G-197A may be closely associated with susceptibility to the development of OA in the Korean population. However, there was no relationship between IL-17F T7488C polymorphism and OA susceptibility.     

Increased initial cement–bone interlock correlates with reduced total knee arthroplasty micro-motion following in vivo service

Aseptic loosening of cemented tibial components in total knee arthroplasty (TKA) has been related to inadequate cement penetration into the trabecular bone bed during implantation. Recent postmortem retrieval work has also shown there is loss of interlock between cement and bone by resorption of trabeculae at the interface. The goal of this study was to determine if TKAs with more initial interlock between cement and bone would maintain more interlock with in vivo service (in the face of resorbing trabeculae) and have less micro-motion at the cement–bone interface. The initial (created at surgery) and current (after in vivo service) cement–bone interlock morphologies of sagittal implant sections from postmortem retrieved tibial tray constructs were measured. The implant sections were then functionally loaded in compression and the micro-motion across the cement–bone interface was quantified. Implant sections with less initial interdigitation between cement and bone and more time in service had less current cement–bone interdigitation (r²=0.86, p=0.0002). Implant sections with greater initial interdigitation also had less micro-motion after in vivo service (r²=0.36, p=0.0062). This work provides direct evidence that greater initial interlock between cement and bone in tibial components of TKA results in more stable constructs with less micro-motion with in vivo service.     

Ultrasound combined with SDF‐1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.     

Lower limb kinematics in individuals with chronic low back pain during walking

Several investigators have suggested the presence of a link between Chronic Low Back Pain (CLBP) and lower limbs kinematics that can contribute to functional limitations and disability. Moreover, CLBP has been connected to postural and structural asymmetry. Understanding the movement pattern of lower extremities and its asymmetry during walking can provide a basis for examination and rehabilitation in people with CLBP. The present study focuses on lower limbs kinematics in individuals with CLBP during walking. Three-dimensional movements of the pelvic, hip, knee and ankle joints were tracked using a seven-camera Qualysis motion capture system. Functional dada analysis (FDA) was applied for the statistical analysis of pelvic and lower limbs motion patterns in 40 participants (20 CLBP and 20 controls). The CLBP group showed significantly different hip motion pattern in the transvers plane, altered knee and ankle motion pattern in the sagittal plane on the dominant side and different hip motion pattern in the transvers and frontal planes on the non-dominant side in comparison with the control group over the stance phase. In terms of symmetry, in the CLBP group, hip and knee moved through a significantly different motion patterns in the transvers plane on the dominant side in comparison with the non-dominant side. In the control group, knee moved through a significantly different motion pattern in the transvers plane on the dominant side in comparison with the non-dominant side. In conclusion, low back pain lead to altered movement patterns of the main joints of lower limbs especially on the dominant side during stance phase. Therefore, care should be taken to examine dominant lower limb movement pattern in CLBP to make a better clinical decision.     

Three-dimensional in vivo kinematics and finite helical axis variables of the ovine stifle joint following partial anterior cruciate ligament transection

Partial anterior cruciate ligament (p-ACL) rupture is a common injury, but the impact of a p-ACL injury on in vivo joint kinematics has yet to be determined in an animal model. The in vivo kinematics of the ovine stifle joint were assessed during ‘normal’ gait, and at 20 and 40 weeks after p-ACL transection (Tx). Gross morphological scoring of the knee was conducted. p-ACL Tx creates significant progressive post-traumatic osteoarthritis (PTOA)-like damage by 40 weeks. Statistically significant increases for flexion angles at hoof-strike (HS) and mid-stance (MST) were seen at 20 weeks post p-ACL Tx and the HS and hoof-off (HO) points at 40 weeks post p-ACL-Tx, therefore increased flexion angles occurred during stance phase. Statistically significant increases in posterior tibial shift at the mid-flexion (MF) and mid-extension (ME) points were seen during the swing phase of the gait cycle at 40 weeks post p-ACL Tx. Correlation analysis showed a strong and significant correlation between kinematic changes (instabilities) and gross morphological score in the inferior-superior direction at 40 weeks post p-ACL Tx at MST, HO, and MF. Further, there was a significant correlation between change in gross morphological combined score (ΔGCS) and the change in location of the helical axis in the anterior direction (ΔsAP) after p-ACL Tx for all points analyzed through the gait cycle. This study quantified in vivo joint kinematics before and after p-ACL Tx knee injury during gait, and demonstrated that a p-ACL knee injury leads to both PTOA-like damage and kinematic changes.     

Targeted regulation of FoxO1 in chondrocytes prevents age‐related osteoarthritis via autophagy mechanism

Autophagy is designated as a biological recycling process to maintain cellular homeostasis by the sequestration of damaged proteins and organelles in plasma and cargo delivery to lysosomes for degradation and reclamation. This organelle recycling process promotes chondrocyte homeostasis and has been previously implicated in osteoarthritis (OA). Autophagy is widely involved in regulating chondrocyte degeneration markers such as MMPs, ADAMSTs and Col10 in chondrocytes. The critical autophagy‐related (ATG) proteins have now been considered the protective factor against late‐onset OA. The current research field proposes that the autophagic pathway is closely related to chondrocyte activity. However, the mechanism is complex yet needs precise elaboration. This review concluded that FoxO1, a forkhead O family protein, which is a decisive mediator of autophagy, facilitates the pathological process of osteoarthritis. Diverse mechanisms regulate the activity of FoxO1 and promote the initiation of autophagy, including the prominent AMPK and Sirt‐2 cellular pathways. FoxO1 transactive is regulated by phosphorylation and acetylation processes, which modulates the downstream ATGs expression. Furthermore, FoxO1 induces autophagy by directly interacting with ATGs proteins, which control the formation of autophagosomes and lysosomes fusion. This review will discuss cutting‐edge evidence that the FoxO–autophagy pathway plays an essential regulator in the pathogenesis of osteoarthritis.