Development Of Early Osteoarthritis Research Articles

Implant survival after primary total hip arthroplasty due to childhood hip disorders Results from the Danish Hip Arthroplasty Registry

Background Childhood hip disorders including acetabular dysplasia, congenital hip dislocation, epiphysiolysis, and morbus Calvé-Legg-Perthes are well-established risk factors for the development of early osteoarthritis of the hip. These patients have an increased risk of undergoing a total hip arthroplasty (THA) operation early in their life. However, there are very few data on implant survival in such patients.Methods We used data from the Danish Hip Arthroplasty Registry to identify patients who had been treated with a primary THA in Denmark between 1995 and 2005. Implant survival during early and late postoperative follow-up (< 6 months and>6 months, respectively) was assessed for patients treated with a primary THA due to childhood hip disorders, and compared with implant survival for THA patients with primary osteoarthritis.Results 56,087 THA procedures included 53,694 (96%) hips with primary osteoarthritis, 890 (1.6%) with acetabular dysplasia, 565 (1.0%) with congenital hip dislocation, 267 (0.5%) with epiphysiolysis, and 404 (0.7%) hips with morbus Calvé-Legg-PerthesPatients with acetabular dysplasia had an increased risk of revision during the 0–6-month postoperative period compared to patients with primary osteoarthritis (adjusted relative risk (RR)=1.9 (95% CI: 1.2–3.1)). These revisions were mainly performed due to dislocation of the THA, providing an adjusted RR of revision due to dislocation of 2.8 (95% CI: 1.6–4.9) compared to patients operated due to primary osteoarthritis. We found no statistically significant differences in risk of revision for the other childhood hip disorder groups during the early postoperative phase. In addition, we found no substantial differences in revision risk during later follow-up (0.5–12 years) for any of the childhood hip disorders compared to patients with primary osteoarthritis.Interpretation We found an encouraging rate of long-term implant survival for patients with childhood hip disorders. The major concern is the increased risk of revision because of dislocation in the first 6 postoperative months for patients with acetabular dysplasia. However, the advent of alternative bearings and the use of large-diameter femoral heads may improve the outcome after primary THA in these patients.

Effects of different molecular weight hyaluronan products on the expression of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis

Hyaluronan or hyaluronic acid (HA) has been used to treat osteoarthritic knees for more than 30 years. Here, we tested the hypothesis that HA with high molecular weight (MW) would have greater effects than HA with low MW on the expression of the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] during early development of osteoarthritis (OA). We compared the levels of MMP-2, MMP-9, urokinase-type PA (u-PA), and PA inhibitor-1 (PAI-1) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without three different MW HA products (Hyalgan and Artz with low MW, and Synvisc with high MW). Gelatin zymography revealed that three different HA products could decrease the secretion of MMP-2 in all tissue cultures and MMP-9 in meniscal and synovial cultures time-dependently. Enzyme-linked immunosorbent assay showed that Artz and Synvisc had significant inhibition on u-PA and PAI-1 levels after 24 h, but Hyalgan did at 96 h. Compared with Hyalgan and Artz, Synvisc provided the greatest ability to inhibit MMP-2, MMP-9, u-PA, and PAI-1 expression. Our studies clearly demonstrate that the therapeutic effects of using HA to treat early OA may be partially dependant on downregulation of the PA/plasmin system and gelatinases expression, which delay the structural progression of the disease. HA with high MW might have a greater ability than that with low MW to offer effective protection for articular cartilage.

Ingeniería de tejidos y osteoartritis

Articular cartilage lesions predispose to the development of early osteoarthritis. Most current surgical techniques give rise to the formation of fibrocartilage with biochemical and biomechanical properties inferior to those or articular cartilage. Tissue engineering could offer a modern alternative to the treatment of these lesions and in this way, prevent the development of early osteoarthritis in young active patients. Different tissue engineering approaches rely on the current use of autologous chondrocytes, or the potential use of mesenchymal stem cells. Other variables rely on the type of scaffold to use such as synthetic biodegradable polymers, fibrin or collagen-derived scaffolds of different sources, bovine, porcine, rat tail, etc, in the form of gels, sponges, mesh, etc, and all of these with or without growth factors. The use of autologous chondrocytes is a reality at the present time, whether injected under a periosteum patch or seeded on collagen. However, most investigators and biotech companies are in search of onestep surgical procedures, for which reason stem cells have to be kept in mind, as well as systems that will allow arthroscopic implantation.

Naproxen, meloxicam and methylprednisolone inhibit urokinase plasminogen activator and inhibitor and gelatinases expression during the early stage of osteoarthritis

BackgroundTo test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). MethodsSamples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). ResultsGelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. ConclusionNaproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.

Does graft choice affect osteoarthritis development in the knee after anterior cruciate ligament reconstruction?

Dear Editor, We congratulate your journal and the authors Sajovic et al. on their valuable study [4]. The authors report that good or excellent results can be obtained in the majority of ACL reconstructions using either patellar tendon or hamstring tendon autografts and both grafts provided good subjective outcomes and objective stability with no significant differences between the grafts at 5 years. ACL reconstructions using either patellar tendon or hamstring tendon autografts are routinely performed all over the world. However, recent studies show that ACL reconstruction, via the use of patellar tendon autograft, causes early osteoarthritis development in the knee, especially if accompanied by meniscal injury [1, 2]. This osteoarthritis develops secondary to a decrease in bone mineral density [3]. That is why, due to decreased harvest-site symptoms and radiographic osteoarthritis, the authors recommend hamstring tendon reconstructions for their patients [1, 2]. In the authors′ study, ACL injury was accompanied by meniscal injury in 39 patient (20 in STG group, 19 in PT group) [4]. Because most patients who have undergone ACL reconstruction are young, we recommend that the surgeon not only considers early complications (patellar fracture, patellar tendon ruptures, anterior knee pain) and midterm differences between graft outcomes, but also considers further complications such as osteoarthritis, which is secondary to patellar tendon autograft. If the surgeon is experienced, STG must be the first choice for ACL reconstruction. We think this information is important to our readers. The authors also stated, in the Results section, that time from injury to operation was 5 months in patients in the patellar tendon group and 6 months in patients in the STG group. However, in Table 1, time from injury to surgery was 23 months (1–60) for PT and 25 months (1–84) for STG. Which one is true?

A tissue engineered osteochondral plug: an in vitro morphological evaluation

Articular cartilage lesions have a poor intrinsic healing potential. The repair tissue is often fibrous, having insufficient biomechanical properties, which could frequently lead to the development of early osteoarthritis. In the last decade, tissue engineering approaches addressed this topic in order to restore joint function with a differentiated and functional tissue. Many biomaterials and techniques have been proposed and some of them applied in clinical practice, even though several concerns have been raised on the quality of the engineered tissue and on its integration in the host joint. In this study, we focused on engineering in vitro a biphasic composite made of cellular fibrin glue and a calcium-phosphate scaffold. Biphasic composites are the latest products of tissue engineering applied to articular cartilage and they seem to allow a more efficient integration of the engineered tissue with the host. However, a firm in vitro bonding between the two components of the composite is a necessary condition to validate this model. Our study demonstrated a gross and microscopic integration of the two components and a cartilage-like quality of the newly formed matrix. Moreover, we noticed an improvement of this integration and GAGs production during the in vitro culture.

Glucosamine sulfate suppresses the expressions of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis

Background Glucosamine sulfate may have an ex vivo inhibitory effect on the plasminogen activator (PA)/plasmin system and gelatinases expression during the early development of osteoarthritis (OA). Methods We compared the levels of urokinase-type PA (u-PA), PA inhibitor-1 (PAI-1) and gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and -9]) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without glucosamine sulfate. Results Gelatin zymography revealed that glucosamine sulfate could suppress MMP-2 secretion in chondral, meniscal and synovial cultures and also decrease MMP-9 production in synovial and meniscal cultures. ELISA data also showed the suppressive effects of glucosamine sulfate on u-PA and PAI-1 production in synovial cultures at 48 h. Conclusions Our data suggest that one of the therapeutic effects of glucosamine sulfate is to down-regulate the expressions of u-PA, PAI-1, MMP-2 and MMP-9 that underlie the destruction of articular cartilage in the early stage of OA, and therefore to delay the joint failure.

What are the risk factors in the development of osteoarthritis following ACL reconstruction?

I would like to comment on the article by J.K. Seon et al. entitled “Osteoarthritis after anterior cruciate ligament reconstruction using apatellar tendon autograft” [4]. The authors investigated the development of osteoarthritis (OA) in patients who had their ACLs reconstructed using patellar tendon autograft. They determined the risk factors of OA to be: patient age over 25 years at the time of the operation, an interval between the injury and reconstruction of greater than 6 months, and additional meniscal injury [4]. As the follow-up period was long, we would like to know if the patients gained weight during follow-up, because weight increase affects the development of OA independently of the surgical procedure. The importance of increased weight and patient education has been reported previously [5]. The authors found no correlation between anterior instability or persistent subluxation and the developmentof OA in the long-term follow-up [4]. There are studies with much longer follow-ups that demonstrate that these factors increase the cartilage damage and thus osteoarthritis, making these people candidates for total knee replacement [1]. In a recent study, it was reported that the decrease of patellar tendon stiffness causes a decrease in bone mineral content and increases OA in patients who had undergone ACL reconstruction using patellar tendon allograft [2]. Although reconstructions using patellar tendon autograft and hamstring autograft gave similar clinical results, patellar tendon autograft is found to pose a greater risk of early development of OA [3]. In conclusion, although additional meniscal lesions, age and late reconstruction were blamed, patellar tendon autograft and an increase in weight are independent risk factors for osteoarthritis following ACL reconstruction.

The orphan G-protein coupled receptor RDC1: evidence for a role in chondrocyte hypertrophy and articular cartilage matrix turnover

RDC1 is a class A orphan G-protein coupled receptor of unknown function. The purpose of this study was to identify compound RDC1 agonists and use these as tools to determine the effect of RDC1 activation in human chondrocytes and cartilage explant tissue. Computational chemistry was employed to build a homology model of the RDC1 receptor. A virtual screen of in-house compounds was then performed and positive hits screened for their ability to invoke a Ca2+ response in a recombinant RDC1 HEK293 cell line, as measured by FLIPR. The effect of RDC1 activation on human chondrocytes and cartilage explant gene expression was determined by quantitative real-time polymerase chain reaction (PCR), and these effects validated as being mediated by RDC1 using siRNA antisense. Tissue expression profiling demonstrated that RDC1 expression was predominant in cartilage tissue. Treatment of human primary chondrocytes with RDC1 agonist induced a Ca2+ response, suggesting the receptor is active in this tissue type. Treatment for 24h with RDC1 agonist led to altered expression of a number of genes associated with chondrocyte hypertrophy and increased matrix degradation in human primary chondrocytes, and elevated total matrix metalloproteinase (MMP) activity in cartilage explant. Transfection with RDC1 siRNA caused a >90% reduction in human primary chondrocyte RDC1 expression and significantly reduced the impact of RDC1 agonist on the previously identified RDC1-regulated genes. RDC1 activation in human chondrocytes and cartilage explant leads to changes in gene expression and activity associated with chondrocyte hypertrophy, angiogenesis and increased matrix degradation, suggesting signalling via the RDC1 receptor may play an important role in the early development of osteoarthritis (OA).

Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament‐transected knee: Association with excitatory amino acid release in the joint dialysate

We previously reported increased release of the excitatory amino acid (EAA) neurotransmitters, glutamate and aspartate, during the early stage of experimental osteoarthritis (OA). Our present objective was to study the effect of intraarticular injection of hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the sham-operated control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group (n = 12) were injected as above with normal saline. The sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment (n = 14). Twenty weeks after surgery, knee joint dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline injections. Intraarticular HA treatment also suppressed synovitis. Moreover, glutamate and aspartate levels were significantly reduced in the HA group compared to the saline group. Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit glutamate and aspartate release in ACLT knee joints, which attenuates the early development of OA.

Tilt and Rotation Correction of Acetabular Version on Pelvic Radiographs

Anteroposterior pelvic radiographs are the gold standard of imaging for mechanical hip problems. However, correct interpretation is difficult because the projected morphologic features of the acetabulum and nearly all routinely used hip parameters depend on individual pelvic position, which can vary considerably during acquisition. We developed software that recreates the projected acetabular rim and the measured hip parameters as if obtained in a standardized orientation. The vertical and horizontal distances between two easy identifiable points were used as indicators of tilt and rotation. These points were the middle of the sacrococcygeal joint and the middle of the upper border of the symphyseal gap. Calibration of the indicators was achieved by means of serial pelvic radiographs of 20 cadaver pelves. Validation of tilt indicator in 100 patients and a theoretical error analysis revealed that for accurate tilt prediction an additional one-time lateral radiograph of the pelvis is mandatory. The computer-assisted method allows standardized evaluation of anatomic morphologic differences of femoral coverage (dysplasia, retroversion), making their clinical relevance for development of early osteoarthritis more valuable.

Detection of Posttraumatic Cartilage Lesions using Magnetic Resonance Imaging (MRI): An experimental Study on Canines

Purpose: The investigation of cartilage lesions in knee joints after knock injuries with Magnetic Resonance Imaging (MRI) over a time period of six months. Materials and Methods: A controlled force form a drop-tower was applied to one knee of 12 normal adult beagle dogs to produce a subchondral bone bruise and soft tissue compression without visible bone fracture. MR images of both knees were acquired at a magnetic field strength of 1.5 T immediately after this defined knock-trauma and again after six months. The images were based on sagittal T1-weighted spin-echo sequence, a T2-weighted turbo-spin-echo sequence with spectral fat-suppression, and a fat suppressed 3D spoiled gradient echo sequence (FLASH®, SPGR). The traumatized joints underwent an arthroscopy immediately after the second MR examination and biopsies of the cartilage were performed. The biopsies were scored histologically (Mankin score of degenerative cartilage lesions). Results: Six months after trauma, ten out of the twelve canines had circumscribed cartilage lesions in the traumatized area of the affected knee joint and nearly all dogs had joint effusions in the affected knee joints. Furthermore, the knees with the most extending bone marrow edema developed high-grad cartilage lesions. All control scans and cartilage biopsies of the contralateral knee joints showed normal findings. Conclusion: Joint trauma causes focal cartilage defects. The described animal model supports the hypothesis that subchondral traumatic lesions such as bone bruises are an important risk factor for early development of osteoarthritis in (knee) joints. Within a few months, severe osteoarthritis could be induced by subchondral bone bruises. Potential etiogenic mechanisms are the damage of subchondral nutrition of hyaline cartilage or changes in the biochemical composition or biomechanic properties of the cartilage.

The Effect of Posterior Cruciate Ligament Deficiency on Knee Kinematics

Background Alteration of the kinematics of the PCL-deficient knee might be a factor in producing the articular damage. Very little is known about the in vivo weightbearing kinematics of the PCL-deficient knee. Hypothesis Isolated rupture of the posterior cruciate ligament alters knee kinematics, predisposing the patient to development of early osteoarthritis. Study Design Case series. Methods Tibiofemoral motion was assessed using open-access magnetic resonance imaging, weightbearing in a squat, through the arc of flexion from 0° to 90° in 6 patients with isolated rupture of the posterior cruciate ligament in one knee and a normal contralateral knee. Passive sagittal laxity was assessed by performing the posterior and anterior drawer tests while the knees were scanned, again using the same magnetic resonance imaging scanner. The tibiofemoral positions during this stress magnetic resonance imaging examination were measured from midmedial and midlateral sagittal images of the knees. Results Rupture of the posterior cruciate ligament leads to an increase in passive sagittal laxity in the medial compartment of the knee (P < .006). In the weightbearing scans, posterior cruciate ligament rupture alters the kinematics of the knee with persistent posterior subluxation of the medial tibia so that the femoral condyle rides up the anterior upslope of the medial tibial plateau. This fixed subluxation was observed throughout the extension-flexion arc and was statistically significant at all flexion angles (P < .018 at 0°, P < .013 at 20°, P < .014 at 45°, P < .004 at 90°). The kinematics of the lateral compartment were not altered by posterior cruciate ligament rupture. The posterior drawer test showed increased laxity in the medial compartment. Conclusion Posterior cruciate ligament rupture alters the kinematics of the medial compartment of the knee, resulting in “fixed” anterior subluxation of the medial femoral condyle (posterior subluxation of the medial tibial plateau). This study helps to explain the observation of increased incidence of osteoarthritis in the medial compartment, and specifically the femoral condyle, in posterior cruciate ligament-deficient knees.

Femoroacetabular Impingement

A multitude of factors including biochemical, genetic, and acquired abnormalities may contribute to osteoarthritis of the hip. Although the pathomechanism of degenerative process affecting the dysplastic hip is well understood, the exact pathogenesis for idiopathic osteoarthritis has not been established. Based on clinical experience, with more than 600 surgical dislocations of the hip, allowing in situ inspection of the damage pattern and the dynamic proof of its origin, we propose femoroacetabular impingement as a mechanism for the development of early osteoarthritis for most nondysplastic hips. The concept focuses more on motion than on axial loading of the hip. Distinct clinical, radiographic, and intraoperative parameters can be used to confirm the diagnosis of this entity with timely delivery of treatment. Surgical treatment of femoroacetabular impingement focuses on improving the clearance for hip motion and alleviation of femoral abutment against the acetabular rim. It is proposed that early surgical intervention for treatment of femoroacetabular impingement, besides providing relief of symptoms, may decelerate the progression of the degenerative process for this group of young patients.

The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis.

To determine if early focal lesions seen in aging exhibit molecular changes in the extracellular matrix that are similar to those seen in osteoarthritis (OA) and to examine the interrelationships between matrix degradation and synthesis and how they relate to cartilage turnover. Condylar cartilage was obtained postmortem from lesion-free joints and from the lesion (where present as well as) from areas adjacent to and remote from the lesion of 31 knees without signs of joint injury (damage to ligaments or menisci). Cartilage was graded histologically and assayed for type II collagen and proteoglycan aggrecan glycosaminoglycan (GAG) contents and turnover (specifically, type II collagen denaturation and its cleavage by collagenase), type II collagen synthesis (C-propeptide [CPII] content), and aggrecan turnover (846 epitope content). To study the degradation of aggrecan reflected by the release of GAG, we cultured cartilage samples from 10 knees. The more degenerated cartilage from the lesion and adjacent area exhibited significantly more collagen cleavage by collagenase than did cartilage remote from the lesion. Type II collagen denaturation and synthesis were also significantly elevated in the lesion and adjacent cartilage, but neither cleavage nor denaturation correlated with synthesis. Type II collagen content decreased with increasing degeneration, with the lowest levels present in the lesion. Collagen content was indirectly related to denaturation and cleavage adjacent to and remote from the lesion and to denaturation within the lesion. Collagen cleavage and denaturation adjacent to and remote from the lesion were directly interrelated. Cartilage from the lesion contained significantly less GAG than did cartilage adjacent to and remote from the lesion. Aggrecan turnover (846 epitope) was also elevated in both the lesion and adjacent cartilage, whereas GAG release was elevated only in the lesion. GAG and 846 epitope contents were interrelated only at sites remote from the lesion. There was also a direct correlation between collagen and GAG contents in the lesion and in adjacent sites. This correlation was also seen between collagen synthesis (CPII) and the 846 epitope. These results demonstrate that lesions seen in aging exhibit molecular changes in matrix turnover similar to those seen in OA articular cartilage at arthroplasty, but not in healthy normal aging cartilage. The direct relationships between type II collagen cleavage and denaturation and the inverse relationship between type II collagen content and cleavage or denaturation implicate collagenase activity and damage to collagen in this loss of collagen during lesion development. The lack of correlation of the increased synthesis with the degradation or content of type II collagen indicates that these aspects of turnover are not coordinated in the pathologic state. However, the direct relationship between collagen and GAG contents in and adjacent to the lesion illustrates the structural interrelationships of collagen and proteoglycan aggrecan molecules. These results suggest that these focal lesions represent the development of early OA and that this involves the progressive damage to articular cartilage surrounding the lesion as part of the process of the development of idiopathic OA.

Can meniscal suture repair in athletes prevent early development of osteoarthritis without compromising the preinjury sports activity level

In a retrospective study we evaluated the outcome of arthroscopic assisted meniscal repair in athletes on different competitive sports levels. Examination included early osteoarthritic changes and full recovery in sports activities. Fifty athletes were followed up with an average of 6,5 years after meniscal refixation from 1984 through 1998. Twenty-three patients had isolated full-thickness meniscal tears, twenty-seven an associated rupture of the anterior cruciate ligament. Preoperative sports levels were evaluated with Tegners score. Reexamination included Lysholm score, IKDC score and Fairbanks score. With no persisting anterior knee instability 86 % of the professional athletes returned to former full sports activities on competitive levels. Noncompetitive athletes returned in all cases (100 %) to their former level. Fairbanks score increased by 0,1 observing minimal osteoarthitic signs. However, persisting anterior knee instability showed on reexamination poor results. Only one third of all athletes were able to return to former activity levels. Osteoarthritic changes were observed in all patients. Professional athletes had the most severe osteoarthritic changes with an increase of 0,8 in the Fairbanks score. The results demonstrate that complete recovery on sports activities is not possible without reconstruction of the anterior cruciate ligament. Isolated meniscal repair shows poor results in persisting anterior knee instability and does not prevent increasing osteoarthritic changes in athletes.

Effects of sodium hyaluronate on experimental osteoarthritis in rabbit knee joints.

The aim of this study was to examine the effects of intraarticular administration of hyaluronan (HA) on cartilage degradation. Using a partial menisectomy model of osteoarthritis (OA) in the rabbit knee, the authors investigated the catabolic and anabolic changes induced by intraarticular injection of HA. To analyze anabolic changes, the authors assessed cell proliferation by measuring [3H] thymidine uptake, and proteoglycan biosynthesis by noting [35S] sulfate incorporation. For catabolic changes, messenger ribonucleic acid (mRNA) expression of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium were detected with reverse transcriptase polymerase chain reaction (RT-PCR). Of significance for blocking the development of early OA in chondrocytes was the finding that total proteoglycan synthesis in the HA treatment group was significantly higher than in the controls. At the mRNA level in cartilage and synovium, HA inhibited MMP-3 and TIMP-1 production in the same way in the HA treatment group, while not affecting MMP-1 production. Thus it can be concluded that HA affects cartilage catabolism and anabolism to prevent the progress of OA.

The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1β(IL-1β), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis

Objective: To assess the influence of intra-articular injection of hyaluronan (HA) on expression of matrix metalloproteinase-3 (MMP-3), interleukin-1β(IL-1β), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium during the process of osteoarthritis (OA).Design: Eighteen mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into two groups. The first group (HA injection group) received 0.3ml of intra-articular HA injections into the ACLT knees 4 weeks after transection, once a week for 5 weeks as per clinical treatment presently utilized. The animals in the second group (no injection group) were not injected after ACLT. At death, 9 weeks following surgery, synovium and cartilage were harvested and total RNA was extracted. Gene expressions of MMP-3, IL-1β and TIMP-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) for each subgroup created according to morphological grade of OA.Results: The extent and grade of cartilage damage in the HA injection group was less severe than in the no injection group. In synovium, expression of MMP-3 and IL-1β mRNA was suppressed in the mild grades of OA in the HA injection group. HA treatment had either no effect on MMP-3 expression in cartilage at all grades of OA or on enhanced MMP-3 and IL-1β expression in synovium at a progressed grade. No effect of HA treatment on TIMP-1 expression was observed in either cartilage or synovium.Conclusions: These results suggest that one of the mechanism of therapeutic effect of HA is down-regulation of MMP-3 and IL-1β in synovium during early development of OA.

ARE THERE LONG-TERM SEQUELAE FROM SOCCER?

A long-term soccer career seems to increase the risk for early development of osteoarthritis in the lower extremity. Soccer constitutes a risk for osteoarthritis in two different ways. First, by the increased risk for knee injuries in soccer, such as meniscus and anterior cruciate ligament injuries; and second, by the high loading on hip and knee joints that occurs in soccer. The risk for these undesirable effects of soccer are higher in top-level players.

Tumor necrosis factor- α (TNF- α) in canine osteoarthritis: Immunolocalization of TNF- α, stromelysin and TNF receptors in canine osteoarthritic cartilage

The presence and distribution of tumor necrosis factor-alpha (TNF-alpha), TNF receptors and stromelysin [matrix metalloproteinase 3 (MMP-3)] in articular cartilage were evaluated in an iatrogenically induced model of osteoarthritis (OA). Eleven adult male dogs were assigned randomly to a control group (N = 4) or an OA group (N = 7). Osteoarthritis was created by surgical transection of the cranial cruciate ligament of one stifle joint. Both femoral condyles were sampled 3 months post-surgery at necropsy and immunohistochemically analyzed for the presence of the aforementioned cytokines and receptors. Chondrocytes stained for TNF-alpha and TNF receptors in control articular cartilage, spanning an area encompassing most of the middle and deep zones. Positive matrical and chondrocytic staining for TNF-alpha, TNF receptors, and stromelysin was present in OA articular cartilage. Staining varied in intensity and distribution and was dependent of the severity of the lesion. Smooth muscle cells of arteries and arterioles (periarticular synovial membrane) were stained for only one (p55) of two TNF receptors; this staining was confined to control tissues. Results indicate that the differential expression of TNF-alpha and its receptors may be important in the normal maintenance of articular cartilage. The increased presence of TNF-alpha and its receptors in articular cartilage with mild osteoarthritic changes suggests a role in the development of early OA. Regulating TNF-alpha may be an important component in the treatment of OA.