膝关节液中Ⅱ型胶原羧基端端肽含量与滑膜炎程度的关系

目的探讨膝关节液中Ⅱ型胶原羧基端端肽(CTX-Ⅱ)含量与滑膜炎程度之间的关系。方法采用ELISA法对膝关节液中CTX-Ⅱ含量进行检测,并在关节镜下利用Ayral滑膜炎评分法和Outerbridge软骨损伤评分法对滑膜炎程度和软骨损伤程度进行评价。结果骨性关节炎关节液中CTX-Ⅱ含量高于非骨性关节炎OA组(t=-7.558,P<0.05);在Ayral滑膜炎评分≥60分组的关节液中CTX-Ⅱ含量高于Ayral滑膜炎评分<60分组(t=-5.113,P<0.05)。将71例膝关节疾病CTX-Ⅱ含量与Ayral滑膜炎评分呈正相关(r=0.706,P<0.05)。结论膝关节液CTX-Ⅱ含量可作为生物标记物反映关节软骨损伤累计程度外,在一定程度上还反映关节滑膜炎程度;膝关节液CTX-Ⅱ含量升高提示滑膜炎程度较重。     

骨性关节炎患者膝关节软骨损伤的关节镜与MRI诊断分级研究

[目的]提出关节镜及核磁共振成像(magnetic resonance imaging,MRI)诊断骨性关节炎(osteoarthrisis,OA)患者膝关节软骨损伤的分级法,探讨MRI在诊断关节软骨损伤中的价值。[方法]回顾性分析行关节镜检查的123例骨性关节炎患者的膝关节术前MRI表现;按部位将膝关节软骨分为6处;根据形态和信号改变,结合损伤部位,将膝关节软骨损伤在关节镜与MRI的表现加以分析并分级;以关节镜所见为参考标准,计算MRI诊断各级软骨损伤的敏感性、特异性、准确性。[结果]在关节镜及MRI上,膝关节软骨损伤均可分为Ⅰ~Ⅳ级;在738处软骨中,损伤505处(68.43%),其中髌股关节最多,外侧胫股关节最少,且损伤以Ⅲ~Ⅳ级为主;关节镜与MRI判断软骨损伤差异具有统计学意义(χ~2=107.52,P<0.001)。MRI诊断软骨损伤总的敏感性、特异性、准确性分别为70.10%、93.13%、77.37%。[结论]骨性关节炎患者膝关节软骨损伤在关节镜及MRI的表现可被分为4级;软骨损伤以髌股关节最多;MRI诊断骨性关节炎软骨损伤的特异性较高,但敏感性和准确性相对较低。     

膝关节液透明质酸含量与关节软骨损伤的关系

目的探讨膝关节液透明质酸含量与关节软骨损伤程度之间的关系.方法采用ELISA法检测膝关节疾病患者102例共104膝的关节液透明质酸含量,并在关节镜下应用Outerbridge关节软骨损伤评分法和Ayral滑膜炎评分法评价膝关节软骨损伤程度和滑膜炎病理变化程度.采用t′检验、方差分析、Spearman相关分析和多元线性回归分析进行统计分析.结果临床诊断为OA组的关节液透明质酸含量较非OA组低(t′=-2.186,P＜0.05).Outerbridge软骨损伤累计评分≥10分组关节液透明质酸含量比Outerbridge软骨损伤累计评分＜10分组低(t′=-2.316,P＜0.05).104膝关节液透明质酸含量除主要与Ayral滑膜炎评分呈正相关(β′A=0.497,P＜0.001)之外,还与Outerbridge软骨损伤累计评分呈负相关(β′O=-0.364,P＜0.001).在Ayral滑膜炎评分≥60分组,关节液透明质酸含量与Outerbridge软骨损伤累计评分呈负相关(β′o=-0.437,P＜0.001),与Ayral滑膜炎评分呈正相关(β′A=0.339,P＜0.01),其中关节软骨累计损伤程度的影响较大.结论关节液透明质酸除主要反映膝关节滑膜炎程度外,在一定程度上还可反映关节软骨累计损伤程度.当滑膜炎较重时,后者则起主导作用.膝关节液透明质酸含量的降低提示关节软骨累计损伤程度较重.     

骨性关节炎关节软骨损伤与修复的研究进展

骨性关节炎曾被认为是一种关节的退行性病变，但近年的研究证实，其病变是由于机械性外伤或炎症等多因素造成关节软骨损伤，而使软骨成分产生自身免疫反应，造成继发性的关节软骨破坏。其机制主要是关节软骨的蛋白多糖合成受到抑制及胶原纤维受到破坏，使软骨丧失其弹性，增加了液压渗透性而使软骨细胞承受的压应力增高，分解酶增加，滑润作用下降而致关节软骨表面破坏。     

关节镜下治疗不同程度软骨退变疗效观察

目的:观察对比关节镜对不同程度软骨退变的近期与远期临床疗效.方法:对38例膝关节骨性关节炎患者进行关节镜镜检后关节镜下关节清理术,术前根据Kellgren-Lawrence分级法进行分级,术后随访半年～3年,采用Lysholm膝关节功能评分标准进行疗效判定.结果:I～III度关节软骨退变病例术后近期与远期优良率无显著性差异; 但IV度关节软骨退变病例术后远期优良率明显低于近期(P<0.05).结论:关节镜治疗II度及III度膝关节骨性关节炎患者具有较好较好的中远期疗效,但对于对于IV度关节软骨退变的骨性关节炎患者,关节镜下灌洗清理术的远期疗效不理想.     

膝关节周围骨挫伤后关节软骨代谢物变化

目的观察膝关节周围骨挫伤后膝关节液中Ⅱ型胶原羧基端端肽(CTX-Ⅱ)含量的变化。方法收集自2006-05—2012-05由MRI确诊单纯骨挫伤69例(骨挫伤组)、膝关节骨性关节炎61例(关节炎组)、下肢骨折髓内钉内固定45例(正常组)的膝关节液,采用免疫组化法对膝关节液中CTX-Ⅱ含量进行检测,评估骨挫伤后膝关节软骨代谢变化。结果骨挫伤组关节液中CTX-Ⅱ的含量为(69 492.67±101.87)ng/ml,关节炎组关节液中CTX-Ⅱ的含量为(61 484.00±301.60)ng/ml,正常组关节液中CTX-Ⅱ的含量为(45 169.42±105.32)ng/ml。骨挫伤组关节液中CTX-Ⅱ含量高于正常组,差异有统计学意义(t=6.456,P0.001);但和关节炎组差异无统计学意义(t=2.228,P=0.315)。结论骨挫伤后膝关节液CTX-Ⅱ含量升高,可能与骨软骨急性损伤后出现降解有关,需要及时制动,避免进一步损伤造成创伤性关节炎。     

膝关节液中生物学标记物Ⅱ型胶原羧基端端肽的检测及临床意义

目的探讨膝关节液中Ⅱ型胶原羧基端端肽（CTX-Ⅱ）含量与关节软骨损伤和滑膜炎两种病变程度的关系。方法采用ELISA法对膝关节骨性关节炎37例患者（骨性关节炎组，即OA组）、膝关节其他疾病34例患者（非OA组）关节液中CTX-Ⅱ含量进行检测，并在关节镜下利用Outerbridge软骨损伤评分法和Ayral滑膜炎评分法对软骨损伤程度和滑膜炎程度进行评价。结果OA组关节液中CTX-Ⅱ含量高于非OA组（t=-7．558，P〈0．05）；Outerbridge软骨损伤累计评分≥10分组关节液CTX-Ⅱ的含量高于Outerbridge软骨损伤累计评分〈10分组（t=-7．235，P〈0．05）；Ayral滑膜炎评分≥60分组关节液CTX-Ⅱ的含量高于Ayral滑膜炎评分〈60分组（t=-5．113，P〈0．05）；71例膝关节疾病患者CTX-Ⅱ含量除主要与Outerbridge软骨损伤累计评分呈正相关外（r=0.743，P〈0．05），还与Ayral滑膜炎评分呈正相关（r=0．706，P〈0．05）；OA组中Out—erbridge软骨损伤累计评分与Ayral滑膜炎评分呈正相关（r=0．418，P〈0．05）；OA组中CTX-Ⅱ含量与Outerbridge软骨损伤累计评分（r=0．533，P〈0．05）和Ayral滑膜炎评分均呈正相关（r=0．522，P〈0．05）。结论膝关节液中CTX-Ⅱ的含量除主要反映关节软骨损伤累计程度外，在一定程度上还反映关节滑膜炎程度；膝关节液CTX-Ⅱ含量升高提示软骨损伤程度较重。     

膝关节OA患者血清和关节液Dickkopf-1水平变化及意义

目的观察膝关节骨性关节炎（0A）患者血清和关节液Dickkopf-1（dkk-1）水平及其与关节损伤程度的关系。方法采用ELISA法测定53例膝关节OA患者廊清和关节液dkk-1水平,并与正常人血清（30例）和膝关节液（15例）进行对比,分析其与膝关节软骨损伤程度的关系。结果骨性关节炎患者血清和关节液dkk-1水平均高于对照组（P均〈0．05）,关节液dkk-1水平升高与膝关节损伤程度成正相关（r=0．442,P〈0．05）。结论血清和关节液dkk-1水平可以作为评价OA患者病情严重程度的一个辅助临床指标。     

白细胞介素1β在膝关节骨性关节炎滑液中临床意义

目的探讨膝关节液内白细胞介素1β(IL-1β)与膝骨性关节炎(OA)关节镜下分级的关系,寻找反映骨关节炎严重程度的生化指标。方法选择膝关节镜及人工膝关节置换的患者40例,其中11例单纯半月板损伤为对照组;OA患者29例为实验组,再根据其软骨损伤程度分为轻、中、重度3组。抽取其膝关节液送检,测量关节液内IL-1β的浓度。结果对照组与实验组IL-1β浓度差异有统计学意义(P<0.01),实验组不同分级组间差异也具有统计学意义(P<0.01)。OA患者关节液中IL-1β的含量与关节镜下OA的严重程度成正相关(r=0.887,P<0.01)。结论 OA患者关节液中IL-1β的含量与关节镜下OA的严重程度成正相关,可有效反应OA严重程度。     

关节镜下治疗膝关节骨性关节炎(221例随访)

目的评价关节镜治疗膝关节骨性关节炎的效果。方法应用关节镜对骨性关节炎进行选择性清理,包括刨削增生挤压滑膜及脂肪垫、游离体摘除、退变撕裂半月板的修整成形、切除影响关节活动和引起疼痛的骨赘、股骨髁间窝的扩大成形、退变剥脱软骨的清理及关节面的修平、软骨下硬化骨的钻孔、阻挡骨赘的切除。结果全部病例经随访5~74个月,平均35.8个月。术后Lysho lm评分平均提高(33.6±19.5)分。结论关节镜手术以其创伤小、痛苦少、不影响将来的关节置换等优点,为膝关节骨性关节炎提供了一个有效的诊断和治疗方法。     

The effect of body mass and physical activity on the development of guinea pig osteoarthrosis

We quantitatively evaluated the morphological and biochemical effects of body mass and physical activity on spontaneously developing guinea pig osteoarthrosis (OA). 6-month-old male guinea pigs were allocated to 3 groups: controls (C) living under standard laboratory conditions with food ad libitum; mobilized animals (M) allowed unrestricted motion in large rooms with food ad libitum; and a diet group (D) weight-matched with the M-group. At 9- and 12-months of age they were killed and the left proximal tibia was processed for quantitative histology and the right tibial articular cartilage for analyses of glycosaminoglycan (GAG). OA mostly occurred on the medial condyleos central part not covered by the meniscus. The thinnest cartilage was found in 12-month-old M-animals (M12), which had 60% of the central cartilage surface affected by lesions that extended down to the mineralized cartilage. C12 had 25% exposed mineralized cartilage and D12, 2%. Subchondral bone density followed the loading patterns N the highest in M12 and lowest in D12. M12 had the lowest cartilage GAG concentrations. Load appears to be a key external factor in guinea pig OA. An increase in physical activity may be chondroprotective in the early phase, but harmful when fibrillations eventually have developed. This is underscored by the extensive OA changes in M12, although these animals weighed about the same as D12 (which had the least extensive OA). Therefore, a reduction in body mass seems to retard the progression of OA in animals, which are mainly subjected to a static load (C12 and D12), but not sufficiently in animals with a more dynamic load (M12). Changes in morphological patterns are paralleled by changes in GAG concentration, which probably reflect the metabolic capacity of the cartilage.     

The effect of body mass and physical activity on the development of guinea pig osteoarthrosis

We quantitatively evaluated the morphological and biochemical effects of body mass and physical activity on spontaneously developing guinea pig osteoarthrosis (OA). 6-month-old male guinea pigs were allocated to 3 groups: controls (C) living under standard laboratory conditions with food ad libitum; mobilized animals (M) allowed unrestricted motion in large rooms with food ad libitum; and a diet group (D) weight-matched with the M-group. At 9- and 12-months of age they were killed and the left proximal tibia was processed for quantitative histology and the right tibial articular cartilage for analyses of glycosaminoglycan (GAG). OA mostly occurred on the medial condyle's central part not covered by the meniscus. The thinnest cartilage was found in 12-month-old M-animals (M12), which had 60% of the central cartilage surface affected by lesions that extended down to the mineralized cartilage. C12 had 25% exposed mineralized cartilage and D12, 2%. Subchondral bone density followed the loading patterns--the highest in M12 and lowest in D12. M12 had the lowest cartilage GAG concentrations. Load appears to be a key external factor in guinea pig OA. An increase in physical activity may be chondroprotective in the early phase, but harmful when fibrillations eventually have developed. This is underscored by the extensive OA changes in M12, although these animals weighed about the same as D12 (which had the least extensive OA). Therefore, a reduction in body mass seems to retard the progression of OA in animals, which are mainly subjected to a static load (C12 and D12), but not sufficiently in animals with a more dynamic load (M12). Changes in morphological patterns are paralleled by changes in GAG concentration, which probably reflect the metabolic capacity of the cartilage.     

Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage

OBJECTIVE: To investigate the relationship between biochemical markers in the synovial fluid of osteoarthritic and contralateral equine joints and gross articular cartilage pathology. DESIGN: Twenty-two horses underwent bilateral arthroscopy of their carpal or metacarpophalangeal joints following recent onset lameness. The degree of cartilage damage in each joint was scored and synovial fluid, from both the clinically affected and the contralateral joint, was collected. Bone specific alkaline phosphatase (BAP), 5D4 epitope of keratan sulphate (KS), total glycosaminoglycans (GAG) and hyaluronan (HA) were measured. RESULTS: The mean age of the horses was 4.1 years and the maximum duration of lameness was three months. Joints examined were midcarpal, antebrachiocarpal and metacarpophalangeal. The median concentration (semi-interquartile range) of BAP was significantly higher in the clinically active joint than in the contralateral joint, 21.75 (6.22) vs. 12.35 (4.07) units, while the other biomarkers measured were significantly lower in the clinically active joint than in the contralateral joint, i.e. KS 8.79 (1.96) microg/ml vs. 16.39 (5.65) microg/ml, KS:GAG ratio 0.19 (0.04) vs. 0.31 (0.10) and HA 741.6 (222) microg/ml vs. 1061.75 (325) microg/ml. BAP was positively (R=0.57), and KS (R=-0.57) and KS:GAG ratio (R=-0.49) were negatively correlated to the degree of cartilage damage within the joint. CONCLUSION: The correlation between articular cartilage damage and synovial fluid BAP and KS imparts validity to their potential use as non-invasive diagnostic aids in equine osteoarthritis (OA). The positive correlation between BAP and cartilage damage suggests that there is a link between bone turnover and cartilage damage in OA.     

膝关节骨关节炎滑液和软骨骨桥蛋白水平与其病变程度的相关性

目的 探讨膝关节骨关节炎(osteoarthritis,OA)患者滑液和关节软骨骨桥蛋白(osteopontin,OPN)水平及其与病变严重程度的关系.方法 随机选取50例膝关节OA患者[男15例,女35例;年龄48～81岁,平均(61.8±7.4)岁]和10名健康对照者[男4例,女6例;年龄59～68岁,平均年龄(63.2±6.0)岁]作为研究对象.采用Mankin评分评价疾病严重程度,Kellgren-Lawrence标准进行放射学分级,酶联免疫吸附法测定关节滑液OPN水平,免疫组化方法测定关节软骨OPN光密度值.结果 OA患者与对照者相比,关节滑液OPN水平[(4519.60±1830.37)pg/ml:(1179.70±303.39)pg/ml)和关节软骨OPN光密度值[(0.60±-0.06):(0.43±0.07)]均明显升高.关节滑液OPN水平与关节软骨OPN表达呈正相关(r=0.411,P=0.003).关节滑液OPN水平与OA病变严重程度(KL分级)呈正相关(r=0.581,P＜0.001).关节软骨OPN表达与OA病变严重程度(Mankin评分)呈正相关(r=0.675,P＜0.001).结论 关节滑液和关节软骨OPN水平与病变严重程度相关.     

Early post-traumatic osteoarthritis-like changes in human articular cartilage following rupture of the anterior cruciate ligament

OBJECTIVE: Injury to the anterior cruciate ligament (ACL) frequently leads to post-traumatic osteoarthritis (OA). In this study we determined whether early degenerative changes characteristic of idiopathic OA are induced in articular cartilage following ACL injury. METHODS: A small sample of femoral articular cartilage was removed at surgery, as part of ACL reconstruction, from a total of 50 patients with ACL injuries. Of these, 28 underwent surgery less than 1 year post-injury. Control cartilages were obtained from the same site from 21 persons at autopsy. All cartilages were examined for molecular changes. The content of type II collagen, its cleavage by collagenases and its denaturation were determined by immunoassay. The total content of glycosaminoglycan (GAG), which is principally aggrecan, was measured colorimetrically. Data were expressed per unit DNA (GAG and collagen content) or as a percentage of total collagen cleaved or denatured. Other cartilages from the same site (8 controls, 12 less than 1 year and 8 more than 1 year post-injury) were frozen sectioned and examined histologically to determine by Mankin grading cartilage degeneration. RESULTS: Histological analyses revealed that control subjects exhibited staining for proteoglycan, which was reduced in some patients following ACL rupture. Degeneration of the articular surface was sometimes observed 1 year after ACL rupture. Although the Mankin grade increased with time after rupture these changes were not significant. Immunoassays, however, revealed an increase in GAG content within 1 year which was maintained after 1 year although no longer significant. No changes in total type II collagen content were observed during the period of study. However, there were significant increases in the denaturation and cleavage of type II collagen less than and more than 1 year post-ACL rupture. Total type II collagen content was directly correlated with GAG content in all three groups, with the significance being weakest at more than 1 year. After 1 year an inverse correlation was observed between total type II collagen content and collagen cleavage as well as denaturation. CONCLUSIONS: These observations reveal that joint instability resulting from ACL injury rapidly results in degenerative changes characteristic of those seen in idiopathic OA at arthroplasty and in experimental OA following ACL surgery. These changes may contribute to the development of post-traumatic OA that is commonly observed following ACL injury. The observations support and extend conclusions from other studies on human and animal articular cartilage and synovial fluids post-ACL injury that have revealed a rapid onset of damage to type II collagen and an initial increase in proteoglycan content characteristic of experimental OA post-ACL injury. This study provides direct evidence for the rapid development of degenerative changes characteristic of OA following ACL injury.     

关节滑液3B3表位检测对软骨早期退变的诊断价值

[目的]骨性关节炎、髌骨软化症病人膝关节滑液中3B3表位含量是否与软骨退变程度相关。[方法]作者改良了竞争性ELISA检测关节滑液3B3表位的方法。抽吸71例膝骨关节炎、57例髌骨软化症病人及10例正常人志愿者的膝关节滑液，用该方法检测关节滑液中3B3表位含量，比较各组之间的差异。[结果]骨性关节炎组及髌骨软化组病人膝关节滑液中3B3表位均比正常人对照明显升高（P〈0．05），而且骨关节炎Ⅱ级关节软骨退变时关节滑液中3B3表位含量明显比Ⅳ级关节软骨退变增高（P〈0．01），而髌骨软骨软化患者Ⅱ、Ⅲ、Ⅳ级软骨退变各组间无明显差异（P〉0．05）。[结论]检测关节滑液中3B3表位含量具有诊断关节软骨退变的价值，尤其适用于骨性关节炎软骨早期退变（Ⅱ级）的诊断。     

Matrix synthesis in mandibular condylar cartilage of aging mice

Osteoarthritic (OA) lesions often develop along the articular surface of mandibular condylar cartilage of aging mice. Metabolic activities of chondrocytes in condylar cartilage of newborn to 18-month-old mice were evaluated morphologically and biochemically in vivo and in vitro. In the period between birth and 3 months of age, marked age-dependent reductions in the number of cells per unit area (-56.43%), in DNA (-64.38%) and in glycosaminoglycan (GAG) (-46.32%) contents were observed. In the same time period, protein content remained almost constant. Reduced rates in the incorporation of [3H]thymidine, [3H]leucine and [35S]sulfate between birth and 3 months of age (-81.60%, -25.98% and -67.75%, respectively) were also observed in vitro. Collagen synthesis was similarly reduced, from 38.70% in newborns to 27.86% in 18-month-old animals. Morphology and autoradiography in mandibular cartilage revealed that the reductions of cellularity and of sulfated macromolecular synthesis appeared to be more pronounced along the articular surface. In this region OA lesions were often observed. It may thus be that the combination of reduced sulfated GAGs and the decreased number of cells in this region could result in tissue with architecture that is less suited to withstanding stress and thus more prone to the development of the typical OA lesions that are seen along the articular surfaces of mandibular cartilage in aged mice.     

Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes

OBJECTIVE: The functional integrity of articular cartilage is determined by a balance between chondrocyte biosynthesis of extracellular matrix and its degradation. In osteoarthritis (OA), the balance is disturbed by an increase in matrix degradative enzymes and a decrease in biosynthesis of constitutive extracellular matrix molecules, such as collagen type II and aggrecan. In this study, we examined the effects of the sulfate salt of glucosamine (GS) on the mRNA and protein levels of the proteoglycan aggrecan and on the activity of matrix metalloproteinase (MMP)-3 in cultured human OA articular chondrocytes. DESIGN: Freshly isolated chondrocytes were obtained from knee cartilage of patients with OA. Levels of aggrecan and MMP-3 were determined in culture media by employing Western blots after incubation with GS at concentrations ranging from 0.2 to 200 microM. Zymography (casein) was performed to confirm that effects observed at the protein level were reflected at the level of enzymatic activity. Northern hybridizations were used to examine effects of GS on levels of aggrecan and MMP-3 mRNA. Glycosaminoglycan (GAG) assays were performed on the cell layers to determine levels of cell-associated GAG component of proteoglycans. RESULTS: Treatment of OA chondrocytes with GS (1.0-150 microM) resulted in a dose-dependent increase in aggrecan core protein levels, which reached 120% at 150 microM GS. These effects appeared to be due to increased expression of the corresponding gene as indicated by an increase in aggrecan mRNA levels in response to GS. MMP-3 levels decreased (18-65%) as determined by Western blots. Reduction of MMP-3 protein was accompanied by a parallel reduction in enzymatic activity. GS caused a dose-dependent increase (25-140%) in cell-associated GAG content. Chondrocytes obtained from 40% of OA patients failed to respond to GS. CONCLUSIONS: The results indicate that GS can stimulate mRNA and protein levels of aggrecan core protein and, at the same time, inhibit production and enzymatic activity of matrix-degrading MMP-3 in chondrocytes from OA articular cartilage. These results provide a cogent molecular mechanism to support clinical observations suggesting that GS may have a beneficial effect in the prevention of articular cartilage loss in some patients with OA.     

Leg lengthening and glycosaminoglycans in the rabbit knee

We investigated the effects of tibial lengthening by callotasis on glycosaminoglycan (GAG) metabolism of the knee articular cartilage in 30 rabbits. The distraction rate was 1 mm per day. On the right side, the daily distraction was in 2 steps, while on the left it was in 120 steps. The animals were divided into 3 subgroups based on length gain; 10, 20, and 30 percent, respectively. The knee joint fluid and medial tibial cartilage were examined by quantitative analysis of the GAG content and/or synthesis. The immunoreactivity for chondroitin sulfate in the cartilage was also examined by immunohistochemistry. For all length gains, the GAG concentration in the synovial fluid was higher on both sides than in controls, with no difference between sides. The GAG content and synthesis in the cartilage on the 2-step side decreased gradually with increasing length. On the 120-step side, the content did not differ from control values in any length gain, and the level of synthesis at 20 and 30 percent lengthening was higher than the control level. Our findings indicate that the alterations in GAG metabolism are attributable to increased mechanical stress on the articular cartilage, suggesting a moderate increase on the 120-step side compared to an excessive one on the 2-step side.