Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA.     

放散式体外冲击波穴位治疗联合中药熏洗治疗老年膝骨关节炎的疗效分析

摘要 目的：评价放散式体外冲击波（rESW）穴位治疗联合中药熏洗在老年膝骨关节炎（KOA）中的应用效果。方法：选入2021年2月~2022年8月我院收治的老年KOA患者76例,根据治疗方法不同分为对照组和观察组,各38例,两组均予以中药熏洗,观察组加用rESW穴位治疗。评价两组的治疗效果、膝关节功能、疼痛程度等指标,并进行统计比较。结果：与治疗前相比,两组治疗2周、治疗4周时的VAS评分明显下降（P＜0.05）,而观察组下降幅度更大,与对照组差异显著（P＜0.05）;两组治疗前Lysholm评分无明显差异（P＞0.05）,而观察组治疗2周、治疗4周时的Lysholm评分显著高于对照组（P＜0.05）;观察组治疗显效率和有效率均显著高于对照组（P＜0.05）;观察组治疗2周、4周时的血清IL-1β、TNF-α和MMP-13水平较对照组低（P＜0.05）。结论：rESW穴位联合中药熏洗治疗老年KOA患者疗效显著,可缓解疼痛症状,改善膝关节功能,控制炎症反应,且操作简单,值得推荐。     

Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland,the gland of the third eyelid and the knee joint

Background aimsMesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs.MethodsAllogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation.ResultsClinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations.ConclusionsThis is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo.     

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

Tissue-engineered fibrocartilage could become a feasible option for replacing tissues such as the knee meniscus or temporomandibular joint disc. This study employed five growth factors (insulin-like growth factor-I, transforming growth factor-beta1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor) in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs had lower biomechanical and biochemical properties than the controls with no growth factors, suggesting a detrimental effect, but the treatment with insulin-like growth factor-I tended to improve the constructs. Additionally, the 6-week time point was consistently better than that at 3 weeks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue.     

Functional role of hedgehog pathway in osteoarthritis

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.     

髋关节骨性关节炎患者生存质量现状及其影响因素分析

目的：探讨髋关节骨性关节炎患者生存质量现状及其影响因素。方法：选择60 例髋关节骨性关节炎患者作为观察组,60 例 健康者作为对照组。采用SF-36 生存质量评价量表,比较观察组与对照组SF-36 量表各维度评分;分析影响患者生存质量的因素。 结果：①观察组SF-36 量表各维度评分均显著低于健康对照组,差异均具有统计学意义（P＜0.05）;②经Pearson 单因素分析, SF-36 量表综合得分在性别、职业、病程、治疗前景、内科慢性疾病数、10m 步行速度及K-L 分级方面的差异均具有统计学意义 （P＜0.05~0.01）;③经多元Logistic 回归分析,病程（beta=0.772,S.E.=0.689,Wald=34.027,P＜0.05,OR=1.99）、治疗前景（beta=0.778,S. E.=0.542,Wald=55.638,P＜0.05,OR=1.88）、内科慢性疾病数（beta=0.929,S.E.=0.301,Wald=12.382,P＜0.05,OR=1.72）、10m 步行速 度（beta=0.661,S.E.=0.381,Wald=19.929,P＜0.05,OR=1.69）及K-L 分级（beta=0.992,S.E.=0.526,Wald=28.371,P＜0.05,OR=2.31）为影 响髋关节骨性关节炎患者生存质量的危险因素。结论：髋关节骨性关节炎患者生存质量明显差于健康者,病程、治疗前景、内科慢 性疾病数、10m步行速度及K-L分级是影响患者生存质量的危险因素。     

Stance and swing phase knee flexion recover at different rates following total knee arthroplasty: An inertial measurement unit study

Total knee arthroplasty (TKA) is the most common joint replacement in the United States. Range of motion (ROM) monitoring includes idealized clinic measures (e.g. goniometry during passive ROM) that may not accurately represent knee function. Accordingly, a novel, portable, inertial measurement unit (IMU) based ROM measurement method was developed, validated, and implemented. Knee flexion was computed via relative motion between two IMUs and validated via optical motion capture (p > 0.05). Prospective analyses of 10 healthy individuals (5M, 50 ± 19 years) and 20 patients undergoing TKA (3 lost to follow up, 10M, 65 ± 6 years) were completed. Controls wore IMUs for 1-week. Patients wore IMUs for 1-week pre-TKA, 6-weeks immediately post-TKA, and 1-week at 1-year post-TKA. Flexion was computed continuously each day (8–12 h). Metrics included daily maximum flexion and flexion during stance/swing phases of gait. Maximum flexion was equal between cohorts at all time points. Contrastingly, patient stance and swing flexion were reduced pre-TKA, yet improved post-TKA. Specifically, patient stance and swing flexion were reduced below control/pre-TKA values during post-TKA week 1. Stance flexion exceeded pre-TKA and equaled control levels after week 2. However, swing flexion only exceeded pre-TKA and equaled control levels at 1-year post-TKA. This novel method improves upon the accuracy/portability of current methods (e.g. goniometry). Interestingly, surgery did not impact maximum ROM, yet improved the ability to flex during gait allowing more efficient and safe ambulation. This is the first study continuously monitoring long-term flexion before/after TKA. The results offer richer information than clinical measures about expected TKA rehabilitation.     

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.     

关节镜下前交叉韧带重建术的手术时机对患者膝关节功能恢复的影响

目的:研究关节镜下前交叉韧带(ACL)重建术的手术时机对患者膝关节功能恢复的影响。方法:选取2016年1月至2017年8月我院收治的膝关节ACL损伤患者65例为研究对象,所有患者均接受关节镜下ACL重建术治疗,并按照患者受伤至接受手术的时间分为研究组(n=35,受伤至接受手术的时间≤3周)和对照组(n=30,受伤至接受手术的时间3周),术后对患者进行为期6个月的随访,对比两组患者术前和术后6个月的膝关节活动度、膝关节功能以及ACL恢复情况,并比较随访期间两组并发症发生情况。结果:术前,两组膝关节活动度、国际膝关节文献委员会膝关节评估表(IKDC)和Lysholm膝关节评分比较差异无统计学意义(P0.05),术后6个月,两组膝关节活动度、IKDC评分和Lysholm膝关节评分均较术前升高,且研究组高于对照组,差异有统计学意义(P0.05)。术前与术后6个月,两组前抽屉(ADT)试验和Lachman试验阴性率比较差异无统计学意义(P0.05),但与术前比较,术后6个月两组ADT试验和Lachman试验阴性率均升高,差异有统计学意义(P0.05)。与对照组比较,研究组并发症总发生率降低,差异有统计学意义(P0.05)。结论:膝关节ACL损伤患者在不同时间内接受关节镜下ACL重建术治疗均具有较好的效果,但是在受伤后3周内接受手术对患者膝关节功能恢复效果更明显,同时并发症发生率也相对更低。