Varus knee osteoarthritis: Elevated synovial CD15 counts correlate with inferior biomechanical properties of lateral‐compartment cartilage

The study analyzed the influence of synovitis on the histological and biomechanical properties of lateral‐compartment cartilage. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included. Osteochondral samples from the distal lateral femur underwent biomechanical and histologic analysis. Synovial tissue was sampled for histological (chronic synovitis score) and immunohistochemical evaluation of the degree of synovitis. CD15 (neutrophils), Ki‐67 (dividing cells), and CD68 (macrophages) were tested in all synovial samples. While the histological synovitis score did not correlate with the degree of cartilage degeneration (histological OARSI grades), both CD15 (r_s = 0.297, p = 0.006) and Ki‐67 (r_s = 0.249, p = 0.023) correlated with histological OARSI grades. There was a weak negative correlation of CD15 with biomechanical properties of cartilage of the distal lateral femur (aggregate modulus (Ha): r_s = ?0.125; p = 0.257; dynamic modulus (DM): r_s = ?0.216; p = 0.048). No correlations were observed for Ki‐67 and CD68. In addition, biomechanical properties were inferior in knees with a CD15 of >8/high power field compared to knees with a CD15 of ≤8/high power field (Ha: p = 0.031, d = 0.46; DM: p = 0.005, d = 0.68). The study demonstrates an association of increased inflammatory activity with advanced cartilage degeneration. Lateral‐compartment cartilage in knees with elevated synovial CD15 counts has a reduced ability to withstand compressive loads. CD15 might serve as an indicator for inferior biomechanical cartilage properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:841–846, 2018.

     

Articular cartilage surface roughness as an imaging‐based morphological indicator of osteoarthritis: A preliminary investigation of osteoarthritis initiative subjects

Current imaging‐based morphometric indicators of osteoarthritis (OA) using whole‐compartment mean cartilage thickness (MCT) and volume changes can be insensitive to mild degenerative changes of articular cartilage (AC) due to areas of adjacent thickening and thinning. The purpose of this preliminary study was to evaluate cartilage thickness‐based surface roughness as a morphometric indicator of OA. 3D magnetic resonance imaging (MRI) datasets were collected from osteoarthritis initiative (OAI) subjects with Kellgren–Lawrence (KL) OA grades of 0, 2, and 4 (n = 10/group). Femoral and tibial AC volumes were converted to two‐dimensional thickness maps, and MCT, arithmetic surface roughness (S_a), and anatomically normalized S_a (normS_a) were calculated. Thickness maps enabled visualization of degenerative changes with increasing KL grade, including adjacent thinning and thickening on the femoral condyles. No significant differences were observed in MCT between KL grades. S_a was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.55 ± 0.10 mm, KL2: 0.53 ± 0.09 mm, KL4: 0.79 ± 0.18 mm), medial femoral condyle (KL0: 0.42 ± 0.07 mm, KL2: 0.48 ± 0.07 mm, KL4: 0.76 ± 0.22 mm), and medial tibial plateau (KL0: 0.42 ± 0.07 mm, KL2: 0.43 ± 0.09 mm, KL4: 0.68 ± 0.27 mm). normS_a was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.22 ± 0.02, KL2: 0.22 ± 0.02, KL4: 0.30 ± 0.03), medial condyle (KL0: 0.17 ± 0.02, KL2: 0.20 ± 0.03, KL4: 0.29 ± 0.06), whole tibia (KL0: 0.34 ± 0.04, KL2: 0.33 ± 0.05, KL4: 0.48 ± 0.11) and medial plateau (KL0: 0.23 ± 0.03, KL2: 0.24 ± 0.04, KL4: 0.40 ± 0.10), and significantly higher in KL2 compared to KL0 in the medial femoral condyle. Surface roughness metrics were sensitive to degenerative morphologic changes, and may be useful in OA characterization and early diagnosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2755–2764, 2017.

     

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression

Cell‐based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1–2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty. Superficial(C_sp, top ～ 500 µm) and deep cartilage(C_dp) was separated. Chondrogenic Connective Tissue Progenitors (CTP‐C) were assayed by standardized Colony‐Forming‐Unit assay using automated image analysis (Colonyze^TM) based on ASTM standard F‐2944‐12. Cell concentration (cells/mg) was significantly greater in C_sp (median: 7,000; range: 3,440–17,600) than C_dp (median: 5,340; range: 3,393–9,660), p = 0.039. Prevalence (CTPs/million cells) was not different between C_sp (median: 1,274; range: 0–3,898) and C_dp (median:1,365; range:0–6,330), p = 0.42. In vitro performance of CTP‐C progeny varied widely within and between patients, manifest by variation in colony size and morphology. Mean histopathological Mankin score was 4.7 (SD = 1.2), representing mild to moderate OA. Tidemark breach by blood vessels was associated with lower C_sp cell concentration (p = 0.02). Matrix degradation was associated with lower C_dp cell and CTP‐C concentration (p = 0.015 and p = 0.095, respectively), independent of articular surface changes. These findings suggest that the initiation of OA may occur in either superficial or deep zones. The pathological changes affect CTP‐Cs in C_sp and C_dp cartilage zones differently. The heterogeneity among the available CTP‐Cs in C_sp and C_dp suggests performance‐based selection to optimize cell‐sourcing strategies for therapy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1728–1738, 2018.

     

自主运动对高脂饮食诱导的肥胖小鼠膝骨关节炎软骨形态学的影响

目的研究高脂饮食诱导的骨性关节炎发生过程中骨关节软骨病变以及自主运动对骨性关节炎软骨的影响机制,探讨自主运动对膝骨关节炎软骨的保护作用,为临床治疗膝骨关节炎提供有效的实验证据。方法将28只C57BL/6 J小鼠随机分为正常饮食组(C-Sed组,n=6)、正常饮食加运动组(C-Ex组,n=6)、高脂饮食组(HF-Sed组,n=8)及高脂饮食加运动组(HF-Ex组,n=8)。C-Sed组和C-Ex组喂养基础饲料(13.5%Kcal),HF-Sed组和HF-Ex组喂养高脂饲料(60%Kcal)。喂养8周后,C-Ex组和HF-Ex组小鼠采用自主转轮运动进行干预,记录运动数据,运动3周后行颈椎脱臼处死;C-Sed组和HF-Sed组小鼠不进行运动干预,继续喂养不同膳食4周后行颈椎脱臼处死,取膝关节软骨组织进行固定、脱钙,制成4μm厚石蜡切片,并进行HE及甲苯胺蓝染色,测量各组小鼠软骨层厚度,探究自主转轮运动对肥胖小鼠膝骨关节炎软骨形态学的影响。结果喂养12周结束后,与C-Sed组小鼠相比,HF-Sed组小鼠体重明显增加,高脂饮食成功诱导了高脂饮食组小鼠发生肥胖,且经HE及甲苯胺蓝染色后,可观察到与C-Sed组小鼠相比,HF-Sed组小鼠软骨表面粗糙、部分缺损,软骨层厚度降低(P0.001);而HF-Ex组较HF-Sed组小鼠关节软骨表面光滑,软骨层厚度增加,Mankin评分分值降低。结论 3周自主转轮运动可增加高脂组小鼠软骨层厚度,降低Mankin评分分值,延缓骨关节炎软骨退变,起到保护关节软骨的作用。     

骨关节炎患者滑液中COMP水平与病情严重程度的相关性研究

背景：软骨寡聚基质蛋白（cartilage oligomeric matrix protein,COMP）是软骨中非胶原蛋白的主要成分,软骨的损伤、修复和代谢变化均可能影响COMP的表达水平。目的：研究骨关节炎（osteoarthritis,OA）患者关节滑液中COMP水平与病变严重程度的相关性,探讨注射玻璃酸钠对关节滑液中COMP的影响。方法：52例膝关节0A患者接受关节内注射玻璃酸钠治疗,治疗前、治疗后6个月行X线片检查,按Kellgren放射学诊断标准评级,记录治疗前和治疗开始后5周、6个月时患者膝关节的WOMAC评分。采用ELISA方法测定在接受透明质酸钠治疗前、治疗开始后5周关节液中的COMP水平。19例因半月板或韧带损伤接受关节镜手术的患者作为正常对照组。结果：OA组患者滑液中COMP水平明显高于对照组,有统计学差异（P=0．036）。OA组患者滑液中COMP水平与OA严重程度（WOMAC评分）呈正相关（P=0．001）,与影像学Kellgren分级标准无相关性（P=0．12）。结论：滑液中COMP水平与OA病变严重程度呈正相关,测定OA患者血中COMP水平对进一步研究OA发病机理、早期发现并采取有效防治策略及监测防治效果具有极其重要的意义。     

Joint instability and cartilage compression in a mouse model of posttraumatic osteoarthritis

Joint instability and cartilage trauma have been previously studied and identified as key mediators in the development of posttraumatic osteoarthritis (PTOA). The purpose of this study was to use an in vivo model to compare the effect of joint instability, caused by the rupture of the anterior cruciate ligament (ACL), versus cartilage compression. In this study, mice were subjected to cyclical axial loads of twelve Newtons (N) for 240 cycles or until the ACL ruptured. One and eight weeks after this procedure, knees were sectioned coronally and evaluated for osteoarthritis by histology. Using a scoring scale established by [Pritzker K, Gay S, Jimenez S, et al. (2006): Osteoarthritis Cartilage 14:13–29], the articular cartilage across each surface was scored and combined to produce a total degeneration score. The ACL‐ruptured group had a significantly greater total degeneration score than either control or compression treated joints at 1 and 8 weeks. Additionally, only sections from ACL‐ruptured knees consistently showed synovitis after 1 week and osteophyte formation after 8 weeks. Thus, it appears using that ACL rupture consistently creates a severe osteoarthritis phenotype, while axial cartilage compression alone does not appear to be an appropriate method of inducing PTOA in vivo. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:318–323, 2014.     

由IL-10/JAK2/STAT3通路探讨养血柔筋方对兔膝骨关节炎软骨损伤的研究

目的 由白细胞介素(IL)-10/Janus激酶(JAK2)/信号传导与转录激活因子3(STAT3)通路探讨养血柔筋方对兔膝骨关节炎(knee osteoarthritis, KOA)软骨损伤的影响及机制。方法 将新西兰雄兔分为空白组、KOA模型组、养血柔筋方组(50 mg/kg)、塞来昔布组(24 mg/kg)、JAK2激活剂组(50 mg/kg养血柔筋方+0.11 mg/kg AG490),每组6只。通过木瓜蛋白酶诱导KOA兔模型，造模成功后给予相应治疗。运用HE染色观察软骨组织病理变化，Mankin评分进行定量评分；透射电镜观察软骨组织的超微结构；ELISA测量血清IL-1β、IL-6含量；免疫组织化学检测软骨组织基质金属蛋白酶13(MMP13)、转化生长因子-β₁(TGF-β₁)、Ⅱ型胶原蛋白(COl-Ⅱ)蛋白表达；Western Blot检测软骨组织IL-10/JAK2/STAT3通路蛋白表达。结果 与空白组比较，KOA模型组中软骨组织病变严重，Mankin评分、IL-1β和IL-6含量、MMP13、p-JAK2和p-STAT3蛋白...     

Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin‐O/fast green staining, matrix metalloproteinase‐13 (MMP‐13), and type X collagen immunohistochemistry, toluidine blue staining, and micro‐CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP‐13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959–1968, 2018.

     

Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population

Articular cartilage calcification is considered a pathological albeit incompletely understood process which is known to be associated with osteoarthritis of the knee and hip. The goal of this study was to determine the prevalence of articular cartilage calcification of the shoulder as a non‐weight‐bearing joint and to analyze the interrelationship of calcification with age and histological severity of shoulder osteoarthritis in the general population. In a cross‐sectional study of 180 humeral heads from 90 donors (n = 49 male, n = 41 female; mean age 62.7 years [20–93]), cartilage calcification of the humeral head was quantified by digital contact radiography (DCR). Histological OA grade (OARSI) was determined and structural equation modeling (SEM) was used to analyze the interrelationship of cartilage calcification, OARSI and age. The prevalence of articular cartilage calcification was 98.9% (95%CI: [93.96%, 99.97%]) and was independent of gender (p = 0.55). Cartilage calcification of one shoulder correlated significantly with that of the contralateral side (r = 0.61, 95%CI: [0.46, 0.73], p < 0.001). SEM demonstrated significant associations between histological OA grade and cartilage calcification (r = 0.55, p = 0.039), between histological OA grade and age (β = 0.59, p < 0.001) but not between age and cartilage calcification (β = 0.24, p = 0.116). In conclusion, the prevalence of shoulder cartilage calcification in the general population is higher than anticipated. The high prevalence, its concomitant bilateral manifestation and the association between the amount of cartilage calcification and OA severity, but not age, suggest that cartilage calcification is a systemically driven process with early onset in life and may be a causative factor in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1984–1990, 2016.     

自体软骨膜、骨膜游离移植修复软骨缺损治疗骨性关节炎

目的：评价自体软骨膜或骨膜游离移植术修复膝关节大面积软骨缺损，治疗膝关节骨性关节炎的疗效。方法：将髌骨及股骨髁，胫骨平台病损软骨清除，游离移植软骨或骨膜修复软骨缺损，治疗骨性关节炎124例，术后不需外固定，4天后持续被动关节活动器作持续动活动。2周后下床活动，结果：术后平均随访6年，治疗效果满意。结论：采用自体软骨膜，骨膜游离移植修复大面积软骨缺损，治疗骨性关节炎，可取得满意效果。     

中药干预软骨细胞外基质降解治疗骨关节炎的研究进展

骨关节炎作为一种退行性骨关节疾病，临床表现为关节疼痛及不同程度的功能障碍。研究表明，骨关节炎的产生多与软骨细胞外基质的过度降解有关。基质金属等蛋白酶的表达对软骨细胞外基质的降解具有促进作用，炎症因子的过度产生可促进蛋白酶的表达及细胞外基质的降解。中药通过干预蛋白酶的表达及抑制炎症因子的产生，对软骨细胞外基质的降解具有抑制作用，进而干预骨关节炎进展。因此，中药运用于临床，一方面可减少现代药物的毒副作用，另一方面由于中药的副作用小等优势也成为独特的治疗优势。该文通过中药干预软骨细胞外基质降解研究现状进行总结，旨在为中药干预骨关节炎提供参考依据，也为中药运用于临床，在治疗骨关节炎方面发挥独特的优势。     

硫酸镁与氯化钠溶液灌洗对创伤性关节炎软骨损伤修复的影响

目的通过股骨髁间钻孔构建兔创伤性关节炎(PTOA)模型,比较相同渗透压下(400 mOsm/L)硫酸镁与氯化钠溶液持续灌洗对PTOA软骨损伤修复的影响。方法对18只新西兰白兔采用股骨髁间钻孔构建PTOA模型,随机分为PTOA组、氯化钠组和硫酸镁组,每组6只。ELISA检测关节腔积液白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、Ⅱ型胶原蛋白(CollagenⅡ)的表达,qPCR检测滑膜组织IL-1β、TNF-α、金属蛋白酶-3(MMP-3)基因表达。行软骨切片染色组织学观察及骨关节炎(OA)评分。结果关节腔积液IL-1β、TNF-α、CollagenⅡ分泌硫酸镁组少于PTOA组和氯化钠组,滑膜组织IL-1β、TNF-α和MMP-3 mRNA水平硫酸镁组低于PTOA组和氯化钠组;软骨组织切片OA评分硫酸镁组低于PTOA组和氯化钠组,差异均有统计学意义(P<0.05)。结论与相同渗透压下氯化钠溶液相比,硫酸镁溶液有利于减轻关节内炎症,减少CollagenⅡ及蛋白聚糖丢失,对软骨退变起到保护作用,有利于延缓PTOA病情进展。     

Mitoprotective therapy preserves chondrocyte viability and prevents cartilage degeneration in an ex vivo model of posttraumatic osteoarthritis

No disease‐modifying osteoarthritis (OA) drugs are available to prevent posttraumatic osteoarthritis (PTOA). Mitochondria (MT) mediate the pathogenesis of many degenerative diseases, and recent evidence indicates that MT dysfunction is a peracute (within minutes to hours) response of cartilage to mechanical injury. The goal of this study was to investigate cardiolipin‐targeted mitoprotection as a new strategy to prevent chondrocyte death and cartilage degeneration after injury. Cartilage was harvested from bovine knee joints and subjected to a single, rapid impact injury (24.0 ±1.4 MPa, 53.8 ± 5.3 GPa/s). Explants were then treated with a mitoprotective peptide, SS‐31 (1µM), immediately post‐impact, or at 1, 6, or 12 h after injury, and then cultured for up to 7 days. Chondrocyte viability and apoptosis were quantified in situ using confocal microscopy. Cell membrane damage (lactate dehydrogenase activity) and cartilage matrix degradation (glycosaminoglycan loss) were quantified in cartilage‐conditioned media. SS‐31 treatment at all time points after impact resulted in chondrocyte viability similar to that of un‐injured controls. This effect was sustained for up to a week in culture. Further, SS‐31 prevented impact‐induced chondrocyte apoptosis, cell membrane damage, and cartilage matrix degeneration. Clinical Significance: This study is the first investigation of cardiolipin‐targeted mitoprotective therapy in cartilage. These results suggest that even when treatment is delayed by up to 12 h after injury, mitoprotection may be a useful strategy in the prevention of PTOA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2147–2156, 2018.

     

Age and obesity alter the relationship between femoral articular cartilage thickness and ambulatory loads in individuals without osteoarthritis

Articular cartilage is sensitive to mechanical loading, so increased risk of osteoarthritis in older or obese individuals may be linked to changes in the relationship between cartilage properties and extrinsic joint loads. A positive relationship has been reported between ambulatory loads and cartilage thickness in young individuals, but whether this relationship exists in individuals who are older or obese is unknown. This study examined the relationship between femoral cartilage thickness and load, measured by weight × height and the peak adduction moment, in young normal‐weight (28 subjects, age: 28.0 ± 3.8 years, BMI: 21.9 ± 1.9 kg/m²), middle‐aged normal‐weight (27 subjects, 47.0 ± 6.5 years, 22.7 ± 1.7 kg/m²), young overweight/obese (27 subjects, 28.4 ± 3.6 years, 33.3 ± 4.6 kg/m²), and middle‐aged overweight/obese (27 subjects, 45.8 ± 7.2 years, 31.9 ± 4.4 kg/m²) individuals. On the lateral condyle, cartilage thickness was positively correlated with weight × height for all groups (R² = 0.26–0.20) except the middle‐aged overweight/obese. On the medial condyle, weight × height was significantly correlated only in young normal‐weight subjects (R² = 0.19), as was the case for the correlation between adduction moment and medial–lateral thickness ratio (R² = 0.20). These results suggest that aging and obesity are both associated with a loss of the positive relationship between cartilage thickness and ambulatory loads, and that the relationship is dependent on the compartment and whether the load is generated by body size or subject‐specific gait mechanics. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:394–402, 2014.     

Electromechanical probe and automated indentation maps are sensitive techniques in assessing early degenerated human articular cartilage

Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early‐stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non‐destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (four pairs of distal femurs and four pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically, (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM), and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses, and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: Region I was macroscopically degenerated, region II was macroscopically normal but adjacent to regions I and III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:858–867, 2017.

     

Evaluation of articular cartilage with quantitative MRI in an equine model of post‐traumatic osteoarthritis

Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post‐traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age‐matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included T₁, T₂, continuous‐wave T_1ρ (CWT_1ρ), adiabatic T_1ρ (AdT_1ρ), and T_2ρ (AdT_2ρ) and relaxation along a fictitious field (T_RAFF). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full‐thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T₁, CWT_1ρ, and AdT_1ρ in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT_1ρ was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin‐locking amplitudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters (ρ = ?0.531 to ?0.757). T₁, low spin‐lock amplitude CWT_1ρ, and AdT_1ρ were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T₁, CWT_1ρ, and AdT_1ρ in evaluation of compositional and structural changes in cartilage.     

Increased expression and activation of cathepsin K in human osteoarthritic cartilage and synovial tissues

Few studies have analyzed Cathepsin K (CatK) expression in human osteoarthritic tissues. We investigated CatK expression and activation in human articular cartilage using clinical specimens. Human osteoarthritic cartilage was obtained during surgery of total hip arthroplasty (n = 10), and control cartilage was from that of femoral head replacement for femoral neck fracture (n = 10). CatB, CatK, CatL, CatS, and Cystatin C (CysC) expressions were evaluated immunohistochemically and by real‐time PCR. Intracellular CatK protein was quantified by ELISA. Intracellular CatK activity was also investigated. Osteoarthritis (OA) chondrocytes were strongly stained with CatK, particularly in the superficial layer and more damaged areas. CatB, CatL, CatS, and CysC were weakly stained. CatK mRNA expression was significantly higher in OA group compared to that in control group (p = 0.043), whereas those of CatB, CatL, CatS, and CysC did not differ significantly. Mean CatK concentration (4.83 pmol/g protein) in OA chondrocytes was higher than that (3.91 pmol/g protein) in control chondrocytes (p = 0.001). CatK was enzymatically more activated in OA chondrocytes as compared with control chondrocytes. This study, for the first time, revealed increased CatK expression and activation in human OA cartilage, suggesting possible crucial roles for it in the pathogenesis of osteoarthritic change in articular cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:127–134, 2016.