Magnetic resonance imaging and ultrasonographic evaluation of the patients with knee osteoarthritis: a comparative study

The objectives of the present work were (1) to establish the prevalence of the abnormalities detected by magnetic resonance imaging (MRI) and ultrasonography (US); and (2) to compare these imaging techniques in detail. The study group consisted of 58 patients with symptomatic knee OA and 16 volunteer control subjects. Knee joint was evaluated for femoral condylar cartilage changes, effusion, synovial thickening and popliteal cysts using MRI and US. All knees with OA had cartilage abnormalities on US examinations and normal cartilage was detected in less than 3% of these knees by MRI. Majority of the knees with OA had effusion using US (70%) or MRI (85%). Synovial thickening observed on US (34%) and MRI (50%) were common in the knees with OA. Popliteal cysts were detected in 40% of the knees with OA using US and 35% using MRI. This study confirmed that there was a significant correlation between the MRI and US techniques for evaluating the cartilage and soft tissue changes in the patients with knee OA. There were more significant differences between the controls and the symptomatic knees which had Kellgren-Lawrence (K-L) grade 2 or more OA for the cartilage and soft tissue abnormalities on MRI and US. The prevalence of cartilage changes, effusion, synovial thickening and popliteal cyst using MRI and US were increased as the radiographic grade of OA increased. US examinations could be an alternative to initial evaluation tool to MRI in patients with knee OA.     

Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the Osteoarthritis Initiative

Objective

To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end‐stage radiographic OA.

Methods

One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight‐bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status.

Results

Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (<1%; minimal SRM ?0.22) and not significantly different from healthy knees. Knees with calculated K/L grade 3 showed substantial loss of cartilage thickness (up to ?2.5%; minimal SRM ?0.35), with OV1 changes being significantly (P < 0.05) greater than those in healthy knees. Calculated K/L grade 4 knees displayed the largest rate of loss across radiographic OA grades (up to ?3.9%; minimal SRM ?0.51), with OV1 changes also significantly (P < 0.05) greater than in healthy knees.

Conclusion

MRI‐based cartilage thickness showed high rates of loss in knees with moderate and end‐stage radiographic OA, and small rates (indistinguishable from healthy knees) in mild radiographic OA. From the perspective of sensitivity to change, end‐stage radiographic OA knees need not be excluded from longitudinal studies using MRI cartilage morphology as an end point.

     

Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis.

OBJECTIVES: To compare plasma levels of matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) between patients with knee osteoarthritis and normal subjects, to investigate whether the degree of knee joint involvement is related to those measurements, and to compare patients with and without generalized osteoarthritis. METHODS: Eighty-three women with knee osteoarthritis (OA patients) were studied. Plasma levels of MMP-3, MMP-9 and TIMP-1 were measured by enzyme immunoassays. Knee and hand radiographs were taken of all patients. The joints of the knee and hand were graded from 0 to 4 according to Kellgren and Lawrence criteria. All OA patients were divided into a generalized OA (GOA) group (n = 37) and a knee OA (KOA) group (n = 46) according to Doherty's criteria. MMPs and TIMP were also measured in 19 normal subjects. RESULTS: Plasma levels of MMP-3 and TIMP-1 were significantly higher in OA patients than in normal subjects. In contrast, MMP-9 was lower in OA patients than in normal subjects. Plasma levels of MMP-3 and MMP-9 were not influenced by the grade of knee OA. TIMP-1 was influenced by the grade of knee OA. Plasma levels of MMP-3 were significantly elevated in GOA compared to KOA. In contrast, there were no significant differences in plasma levels of MMP-9 and TIMP-1 between GOA and KOA. CONCLUSION: Since the plasma level of MMP-3 in GOA was higher than that in KOA patients, it may be a superior indicator for whole-joint degeneration.     

壳聚糖膝关节腔内注射疗法对兔骨关节炎关节软骨的影响

目的观察关节内注射羧甲基壳聚糖(CMCTS)对兔骨关节炎(OA)关节软骨退变及软骨基质金属蛋白酶(MMP)-1,-3mRNA表达的影响。方法24只大耳白兔行单侧膝关节前交叉韧带切断术,术后5周将动物随机分为3组,A组关节内注射2%CMCTS0.3ml,每2周1次;B组关节内注射1%透明质酸钠(HA)0.3ml,每周1次;C组关节内不注射药物。术后11周处死动物,观察各组股骨内髁关节软骨的大体变化,采用反转录-聚合酶链反应(RT-PCR)方法检测股骨内髁退变软骨中MMP-1和MMP-3的mRNA表达。结果CMCTS和HA注射组软骨退变程度较不用药组明显减轻,CMCTS注射组软骨MMP-1、MMP-3的mRNA表达明显低于HA注射组和不用药组。HA注射组软骨MMP-1和MMP-3的mRNA表达与不用药组比较,差异没有显著性意义。结论CMCTS能够明显抑制OA软骨MMP-1和MMP-3的mRNA表达,明显减轻软骨退变的程度,CMCTS对早期OA软骨有修复保护作用。     

Serum levels of collagenase,stromelysin-1, and timp-1

Objective. To measure serum levels of collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in normal subjects and in patients with osteoarthritis (OA), and to assess how these correlate with biochemical and clinical indicators of disease activity in OA. Methods. Specific immunoassays were used to measure MMPs, TIMP-1, and antigenic keratan sulfate (KS). The total area of cartilage affected by the disease was measured (expressed as an articular index). Results. In the normal population (n = 118), the serum concentration of MMP-3, but not of MMP-1 or TIMP-1, increased with age and was approximately 2 times higher in males than in females. In the OA patients (n = 33), the serum levels of MMP-3, but not of MMP-1 or TIMP-1, were significantly elevated and correlated strongly with the articular index but poorly with objective and subjective functional capacity scores as well as with serum levels of antigenic KS and systemic parameters of inflammation. Conclusion. These findings illustrate the importance of matching patients and normal controls for age and sex in further studies of MMP-3 and are consistent with the hypothesis that MMP-3 might play an important role in the degradation of joint cartilage in OA. Further, serum levels of MMP-3 may prove useful for monitoring therapy for OA.     

Femorotibial subchondral bone area and regional cartilage thickness: A cross‐sectional description in healthy reference cases and various radiographic stages of osteoarthritis in 1,003 knees from the Osteoarthritis Initiative

Objective

To identify structural differences in total subchondral bone area (tAB) and cartilage thickness between healthy reference knees and knees with radiographic osteoarthritis (OA).

Methods

Baseline magnetic resonance images from 1 knee of 1,003 Osteoarthritis Initiative participants were studied: 112 healthy reference knees without radiographic OA, symptoms, or risk factors; 70 preradiographic OA knees (calculated Kellgren/Lawrence [K/L] grade 0/1); and 821 radiographic OA knees (calculated K/L grade ≥2). Means and standard (Z) scores (SD unit differences compared with normal subjects) of the tAB and regional cartilage thickness were assessed in the weight‐bearing femorotibial joint and compared between groups.

Results

In men, tAB was 8.2% larger in preradiographic OA knees and 6.6%, 8.1%, and 8.5% larger in calculated K/L grade 2, 3, and 4 radiographic OA knees, respectively, than in reference knees. In women, the differences were +6.8%, +7.3%, +9.9%, and +8.1%, respectively. The external medial tibia showed the greatest reduction in cartilage thickness (Z scores ?5.1/?5.6 in men/women) with Osteoarthritis Research Society International medial joint space narrowing (JSN) grade 3, and the external lateral tibia (Z scores ?6.0 for both sexes) showed the greatest reduction with lateral JSN grade 3. In all subregions of end‐stage radiographic OA knees, ≥25% of the average normal cartilage thickness was maintained. An overall trend toward thicker cartilage was found in preradiographic OA and calculated K/L grade 2 knees, especially in the external central medial femur.

Conclusion

tABs were larger in preradiographic OA and radiographic OA knees than in healthy reference knees, and the difference did not become larger with higher calculated K/L grades. Specific subregions with substantial cartilage thickening or thinning were identified in pre‐, early, and late radiographic OA.

     

Ultrasonographic assessment of pes anserinus tendon and pes anserinus tendinitis bursitis syndrome in patients with knee osteoarthritis

Abstract

Objective. The aim of this study was to assess the ultrasonographic (US) findings of pes anserinus tendon and bursa in patients with knee osteoarthritis (OA) with or without clinical pes anserinus tendinitis bursitis syndrome (PATBS).

Methods. A total of 157 female patients with the diagnosis of knee OA on both knees (314 knees), and 30 age, and body mass index- matched healthy female controls without knee pain (60 knees), were included in the study. PATBS was clinically diagnosed. US evaluation parameters were the measurement of the thickness of pes anserinus tendon insertion region (PA) and examination of the morphologic intratendinous PA tissue characteristics and pes anserinus bursitis (PAB). Radiographic knee osteoarthritis graded I-IV according to Kellgren and Lawrence (KL) for each knee was recorded. Pain and functional status were assessed by the Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results. There were 183 PATBS (58.3%) clinical diagnoses among the 314 knees with OA. The mean thickness of PA in the patients with knee OA graded 1,2,3,4 with/without PATBS was significantly greater than the controls (p = 0.001). The mean thickness of PA in knees with OA KL graded 3 and 4 with/without PATBS, was greater than knees with OA KL graded 1 and 2 with/without PATBS (p < 0,05) (except knee OA KL graded 2 with PATBS versus knee OA KL graded 4 without PATBS).The knee OA KL graded 1,2,3,4 with PATBS had significantly more PAB and less loss of normal fibrillar echotexture of PA compared to controls and knees with OA KL graded 1,2,3,4 without PATBS (p < 0.05). The VAS scores of knees with OA KL graded 3, 4 with PATBS were significantly greater than those of knees with OA KL graded 3,4 without PATBS (p < 0.05). PA thickness was significantly associated with the KL grade (r: 0.336, p:0.001) and PATBS (r: 0.371, p < 0.001).

Conclusion. It is concluded that the mean thickness of PA in knees with OA with/without PATBS was significantly greater than the controls. The mean thickness of PA in knees with OA, KL graded 3 and 4 with/without PATBS, was greater than in knees with OA KL graded 1 and 2 with/without PATBS. The knee OA with PATBS had significantly more PAB, less loss of normal fibrillar echotexture of PA, and higher VAS scores compared to the knees with OA without PATBS. US can serve as a useful diagnostic tool for detection of PATBS in knee OA.     

Relationship between osteoprotegerin/osteoclastogenesis inhibitory factor concentration in synovial fluid and disease severity in individuals with osteoarthritis of the knee

We studied the relationship between osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) concentration in synovial fluid from individuals with osteoarthritis (OA) of the knee and the severity of this condition. The study population included 111 Japanese women with knee OA (153 knees) and 23 normal controls. Osteoarthritic changes were graded according to the system of Kellgren and Lawrence. The concentration of OPG/OCIF in synovial fluid increased with severity of knee OA and was significantly higher in individuals with OA of grade IV than in those with OA of grade 0 or grade 1. It has been shown in a previous study that administration of OPG/OCIF prevents cartilage destruction in adjuvant-induced arthritis in rats. The increase in the concentration OPG/OCIF in synovial fluid of individuals with knee OA might thus reflect a compensatory response to degeneration of articular cartilage and serve to protect cartilage rather than be a cause of OA.     

Correlation of magnetic resonance imaging–based knee cartilage T2 measurements and focal knee lesions with body mass index: Thirty‐six–month followup data from a longitudinal,observational multicenter study

Objective

To compare magnetic resonance imaging (MRI)–based knee cartilage T2 measurements and focal knee lesions and 36‐month changes in these parameters among knees of normal controls and knees of normal weight, overweight, and obese subjects with risk factors for knee osteoarthritis (OA).

Methods

A total of 267 subjects ages 45–55 years from the Osteoarthritis Initiative database were analyzed in this study. Two hundred thirty‐one subjects had risk factors for knee OA, but no radiographic OA (Kellgren/Lawrence score ≤1) at baseline. Thirty‐six subjects were normal controls. Subjects with OA risk factors were stratified in 3 groups: normal weight (n = 78), overweight (n = 84), and obese (n = 69). All subjects underwent 3T MRI of the right knee at baseline and after 36 months. Focal knee lesions were assessed and cartilage T2 measurements (mean T2 and T2 texture analysis) were performed.

Results

The baseline prevalence and severity of meniscal and cartilage lesions were highest in obese subjects and lowest in normal controls (P < 0.05). Obese subjects had the highest mean T2 values and the most heterogeneous cartilage (as assessed by T2 texture analysis), while normal controls had the lowest mean T2 values and the most homogeneous cartilage at baseline (P < 0.05). Increased body mass index (BMI) was significantly (P < 0.05) associated with greater progression of cartilage lesions and constantly elevated cartilage T2 entropy over 36 months.

Conclusion

In preclinical OA, increased BMI is associated with more severe cartilage degeneration as assessed by both morphologic and quantitative MRI measurements.     

Effects of dehydroepiandrosterone on articular cartilage during the development of osteoarthritis

OBJECTIVE: To investigate the in vivo effects of dehydroepiandrosterone (DHEA) on knee joints during the development of experimentally induced osteoarthritis (OA). METHODS: Twenty-two mature NZW rabbits underwent bilateral anterior cruciate ligament transection (ACLT) and received 0.3-ml intraarticular injections of DHEA (at a concentration of 100 microM in phosphate buffered saline) and control solution in the right and left knees, respectively, beginning 4 weeks after ACLT and continuing once weekly for 5 weeks. All animals were killed 9 weeks after surgery, and the knee joints were assessed by gross morphologic, histologic, histomorphometric, and biochemical methods. RESULTS: Gross morphologic inspection following India ink application showed that the right femoral condyles, which received DHEA, demonstrated less severe cartilage damage than did the contralateral condyles. The thickness, area, and roughness of the DHEA-treated femoral condyles provided evidence of a cartilage-protecting effect of DHEA following ACLT. These results were supported by gene expression analysis. Messenger RNA expression of a proinflammatory cytokine, interleukin-1beta, and catabolic enzymes, matrix metalloproteinases 1 and 3, was reduced in the cartilage of the DHEA-treated knee joints, and expression of tissue inhibitor of metalloproteinase 1 was increased. CONCLUSION: Results of the present study demonstrate a cartilage-protecting effect of DHEA during the development of OA following ACLT in a rabbit model.     

Anteroposterior and varus–valgus laxity of the knee increase after stair climbing in patients with mild osteoarthritis

The aim of this study was to measure exercise-induced changes in knee joint laxity in patients with knee osteoarthritis (OA). The study subjects were 46 female patients with OA and 22 age- and sex-matched normal controls. Radiographs of the knee were taken in all subjects, and the disease severity was graded according to the Kellgren and Lawrence (K-L) grading system. The K-L grade of the control subjects (non-OA group) was 0-1. The OA patients were divided into those with mild OA (K-L grade 2, n = 20) and advanced OA (K-L grade 3-4, n = 26). The subject climbed up and down 8 steps on a staircase apparatus over a period of 10 min. The anteroposterior (A-P) translation was measured with KT2000 arthrometer, and varus-valgus (V-V) rotation was measured on stress radiographs before and after the stair climbing. The Δchange in A-P translation after the exercise was significantly larger in mild OA group than other groups (P < 0.005). The Δchange in V-V rotation after exercise was significantly larger in mild and advanced OA groups than the control (P < 0.003). There were no significant differences in A-P laxity and V-V laxity before exercise among the non-OA, mild OA and advanced OA groups. Exercise resulted in significant changes in A-P knee joint laxity in patients with mild OA relative to the control. The results suggest that daily physical activities (e.g., knee bending or squatting) play a role in the development of knee laxity, particularly in patients with mild OA, and that progression of knee OA seems to correlate with increments of A-P knee joint laxity.     

Joint space width measures cartilage thickness in osteoarthritis of the knee: high resolution plain film and double contrast macroradiographic investigation.

OBJECTIVE--To test reliability of joint space width (JSW) measurements as a predictor of cartilage thickness in knees of patients with osteoarthritis (OA), using high definition microfocal radiography. METHOD--JSW was measured from weight bearing plain film macroradiographs taken in the tunnel view and compared with the sum of femoral and tibial cartilage thicknesses measured from double contrast macroarthrograms of the same regions of the same knees obtained in the non-weight bearing lateral position. RESULTS--All knees had medial compartment OA. Comparison of the JSW with the sum of the tibial and femoral cartilage thicknesses revealed a highly significant correlation (p < 0.0001) between the two measurements in the medial but not the lateral compartment. In the middle region of both compartments, JSW was smaller than the cartilage thickness, indicating that, on standing, the curvature of the femoral condyles compressed the cartilage in this region. CONCLUSIONS--JSW reliably measured cartilage thickness in the medial but not the lateral compartment of knees with medial compartment OA. Depending upon the stage of OA disease, JSW reliably reflects cartilage thinning and compression.     

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis

OBJECTIVE: Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The objective of this study was to define the steady state levels of seven different MMPs and two tissue inhibitors of metalloproteinases (TIMPs) as well as the potential metalloproteinase activity in the synovial fluid (SF) to provide more insight into the role of MMPs in cartilage destruction in RA and OA. METHODS: Levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, TIMP-1, and TIMP-2 in SF aspirated from knee joints of 97 patients with RA and 103 patients with OA were measured by the corresponding one step sandwich enzyme immunoassays. Proteolytic activity of MMPs in these SFs was examined in an assay using [(3)H]carboxymethylated transferrin substrate in the presence of inhibitors of serine and cysteine proteinases after activation with p-aminophenylmercuric acetate (APMA). Destruction of RA knee joints was radiographically evaluated. RESULTS: Levels of MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 were significantly higher in RA SF than in OA SF. MMP-7 and MMP-13 were detectable in more than 45% of RA SFs and in less than 20% of OA SFs, respectively. Among the MMPs examined, MMP-3 levels were extremely high compared with those of other MMPs. Direct correlations were seen between the levels of MMP-1 and MMP-3 and between those of MMP-8 and MMP-9 in RA SF. Although the levels of MMP-1 and MMP-3 increased even in the early stage of RA, those of MMP-8 and MMP-9 were low in the early stage and increased with the progression of RA. Molar ratios of the total amounts of the MMPs to those of the TIMPs were 5.2-fold higher in patients with RA than in OA, which was significant. APMA-activated metalloproteinase activity in SF showed a similar result, and a direct correlation was seen between the molar ratios and the activity in RA SF. CONCLUSIONS: Our results show that high levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and TIMP-1 are present in RA SF and suggest that once these MMPs are fully activated, they have an imbalance against TIMPs, which may contribute to the cartilage destruction in RA.     

Cartilage thickening in early radiographic knee osteoarthritis: A within‐person,between‐knee comparison

Objective

To determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within‐person, between‐knee cross‐sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight‐bearing medial femoral condyle (ecMF) and external weight‐bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.

Methods

Both knees of 61 Osteoarthritis Initiative participants (n = 4,796) displayed definite tibial or femoral marginal osteophytes and no JSN in 1 knee, and no signs of radiographic osteoarthritis (OA) in the contralateral knee; this was confirmed by an expert central reader. In these participants, cartilage thickness was measured in 16 femorotibial subregions of each knee, based on sagittal double‐echo steady‐state with water excitation magnetic resonance images. Location‐specific joint space width from fixed‐flexion radiographs was determined using dedicated software. Location‐specific associations of osteophytes with cartilage thickness were evaluated using paired t‐tests and mixed‐effects models.

Results

Of the 61 participants, 48% had only medial osteophytes, 36% only lateral osteophytes, and 16% bicompartmental osteophytes. The knees with osteophytes had significantly thicker cartilage than contralateral knees without osteophytes in the ecMF (mean ± SD +71 ± 223 μmoles, equivalent to an increase of +5.5%; P = 0.015) and ecLF (mean ± SD +64 ± 195 μmoles, +4.1%; P = 0.013). No significant differences between knees were noted in other subregions or in joint space width. Cartilage thickness in the ecMF and ecLF was significantly associated with tibial osteophytes in the same (medial or lateral) compartment (P = 0.003).

Conclusion

The knees with early radiographic OA display thicker cartilage than (contralateral) knees without radiographic findings of OA, specifically in the external femoral subregions of compartments with marginal osteophytes.     

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs

OBJECTIVE: To evaluate the in vivo therapeutic effect of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on the development of lesions in a guinea pig model of osteoarthritis (OA), and to determine the influence of pioglitazone on the synthesis of matrix metalloproteinase 13 (MMP-13) and interleukin-1beta (IL-1beta) in articular cartilage. METHODS: The OA model was created by partial medial meniscectomy of the right knee joint. The guinea pigs were divided into 4 treatment groups: unoperated animals that received no treatment (normal), operated animals (OA guinea pigs) that received placebo, OA guinea pigs that received oral pioglitazone at 2 mg/kg/day, and OA guinea pigs that received oral pioglitazone at 20 mg/kg/day. The animals began receiving medication 1 day after surgery and were killed 4 weeks later. Macroscopic and histologic analyses were performed on the cartilage. The levels of MMP-13 and IL-1beta in OA cartilage chondrocytes were evaluated by immunohistochemistry. RESULTS: OA guinea pigs treated with the highest dosages of pioglitazone showed a significant decrease, compared with the OA placebo group, in the surface area (size) and grade (depth) of cartilage macroscopic lesions on the tibial plateaus. The histologic severity of cartilage lesions was also reduced. A significantly higher percentage of chondrocytes in the middle and deep layers stained positive for MMP-13 and IL-1beta in cartilage from placebo-treated OA guinea pigs compared with normal controls. Guinea pigs treated with the highest dosage of pioglitazone demonstrated a significant reduction in the levels of both MMP-13 and IL-1beta in OA cartilage. CONCLUSION: This is the first in vivo study demonstrating that a PPARgamma agonist, pioglitazone, could reduce the severity of experimental OA. This effect was associated with a reduction in the levels of MMP-13 and IL-1beta, which are known to play an important role in the pathophysiology of OA lesions.     

Use of joint fluid analysis for determining cartilage damage in osteonecrosis of the knee

OBJECTIVE: To assess the value of joint fluid analysis for determining cartilage degradation and prognosis in spontaneous osteonecrosis (ON) of the knee. METHODS: Synovial fluid was obtained from 30 knees with spontaneous ON (26 medial femoral condyles, 4 medial tibial plateaus) as well as from 50 knees with medial compartmental osteoarthritis (OA) as a control. Levels of chondroitin 6-sulfate (C6S), C4S, and hyaluronic acid were measured with high-performance liquid chromatography. The lesion size, appearance of the articular cartilage, and results of magnetic resonance imaging (MRI) were compared with the results of joint fluid analysis. RESULTS: The mean +/- SD level of C6S was 82.2 +/- 36.6 nmoles/ml in joint fluid from ON knees, which was significantly higher than the levels in knees with grade 2 (47.2 +/- 20.0 nmoles/ml) and grade 3 (55.8 +/- 29.2 nmoles/ml) OA. The C6S:C4S ratio was highest in lesions with mild articular changes and reflected the macroscopic alteration of cartilage overlying the ON lesion. The concentration of C6S in the 9 knees with lesions that covered > or = 40% of the condyle (99.0 +/- 32.9 nmoles/ml) was higher than that in the 17 knees with lesions that covered <40% of the condyle (67.2 +/- 31.7 nmoles/ml). Knees with bone marrow edema on MRI had a higher level of C6S than did knees with a fibrous-like appearance. CONCLUSION: While radiologic staging was useful for indicating the size of the ON lesion, it was less valuable for determining articular cartilage damage. Joint fluid analysis may provide more precise information about articular cartilage degradation in ON, and the findings may also be of prognostic significance.     

Effect of dehydroepiandrosterone on cartilage and synovium of knee joints with osteoarthritis in rabbits

The aim of this study was to investigate the effects of intra-articular injection of dehydroepiandrosterone (DHEA) on cartilage and synovium of knee joints with osteoarthritis (OA) in rabbits and the underlying mechanism. Forty rabbits underwent unilateral anterior cruciate ligament transaction and were divided into two groups. Rabbits were injected with 100 μmol/l DHEA dissolved in the dimethylsulphoxide (DMSO) in the knee joints 5 weeks after transaction, once a week for 5 weeks. Rabbits injected with DMSO under the same condition were served as a control. All rabbits were killed 1 week after the last injection. The knee joints were evaluated by gross morphology, histology, and gene expression analysis. Gross morphologic inspection and histological evaluation showed that the DHEA group appeared less damage in cartilage and synovium as compared with the control. Gene expression analysis revealed that the mRNA expression of matrix metalloproteinase-3 (MMP-3) in cartilage and synovium decreased significantly in the DHEA group and that of tissue inhibitor of metalloproteinase-1 (TIMP-1) increased. No significant difference of interleukin-1 beta (IL-1β) mRNA expression was found in the cartilage between two groups while the mRNA expression of IL-1β in the synovium was largely suppressed in the DHEA group. The study suggests that DHEA plays a protective role against cartilage degradation and synovium inflammation in rabbits with OA. This role may be achieved through the regulation of the MMP-3, TIMP-1, and IL-1β gene expression in the cartilage and synovium.     

Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis

Objective:To study the effect of low intensity pulsed ultrasound(LIPUS) on the expression of tissue inhibitor of metalloproteinase-2(TIMP-2) in the serum and expression of matrix metallopeptidase 13(MMP-13) in the articular cartilage cells of rabbits with knee osteoarthritis(OA).Methods:Inner patellar ligament defect method was used to establish the model of knee OA.Four weeks after the modeling,the arterial blood was drawn from the ear of each rabbit,while ELISA was employed to detect the expression of TIMP-2 in the serum.The chondrocytes were separated from animals in each group and then cultured in vitro.All rabbits were divided into control group,OA model group and OA + LIPUS group.Cells in the control and OA groups were not treated,while cells in the OA+ LIPUS group were treated with LIPUS(40 mW/cnr.1 time/day).Cells were collected 7 d later and the RNA and total protein were extracted respectively.Real-time PCR and Western blotting were employed to analyze the expression of MMP-13 in chondrocytes at the mRNA and protein level,respectively.Results:The success rate of establishment of OA model was 83%.The results of ELISA showed that the content of TIMP-2 in the serum of animals with OA was 22.3%,lower than the one in the control group(P0.05).Compared with the normal control group,the expression of TIMP-2in the OA model group was significantly increased,while the expression of MMP-13 was significantly increased(P0.05).After the stimulation of LIPUS,the expression of TIMP-2 and MMP-13 was close to the one in the normal control group.Conclusions:The inner patellar ligament defect method is a mature method to establish the rabbit OA model,with high success rate.The expression of serum TIMP-2 in the OA model group is significantly decreased.LIPUS can up-regulate TIMP-2 and down-regulate MMP-13.