Course Of Osteoarthritis Research Articles

Osteoarthritis and the role of corticosteroid injections: The four groups

Background: Corticosteroid injections are commonly used in the treatment of pain in osteoarthritis. A question that is frequently asked is ‘how many corticosteroid injections can be used’ and the answers given appear to be empirical.Aim: To determine how many corticosteroid injections should be used in osteoarthritis.Methods: PubMed was used to identify articles using terms appropriate to each heading. We reviewed the clinical course of osteoarthritis with evidence from studies of pain and function, radiology, inflammation, and biomechanics. We reviewed possible pain mechanisms and the evidence for the effects and side effects of corticosteroid injections. The conclusions were drawn from an evaluation of the information presented.Results: The reviews led to a classification of osteoarthritis into four groups: improvement, slow/non-progression (the largest group), rapid progression, and chronic pain, and to an evidence-based recommendation for use of corticosteroid injections in each of the four groups.Con...

Is mesenchymal stem cell helpful in early osteoarthritis knee?

Event Abstract Back to Event Is mesenchymal stem cell helpful in early osteoarthritis knee? Aditya Aggarwal1, Sreekanth R. Rajoli1, Vivekanand Jha1 and Mahesh Prakash1 1 Post Graduate Institute of Medical Education & Research, Orthopaedics, Stem Cell Research Facility, Radiodiagnosis, India Introduction: There is no effective therapy available today that alters the pathobiologic course of osteoarthritis. Recent advances have shown Mesenchymal stem cells to be a potential disease modifying treatment. Considering the tissue differentiation property and vast paracrine effects of MSCs we proposed the present study to find out the safety and efficacy of MSCs in osteoarthritis of knee joint. Methods: 12 patients with grade 1and2 bilateral osteoarthritis knee (Ahlbacks radiological grading) were selected. 8-10 ml of bone marrow was aspirated under strict aseptic precautions from the iliac spine. After the stem cell culture and expansion for 4-6 weeks the MSC suspension in 10xPBS was injected directly into the 24 knees by lateral approach. The outcome was evaluated by modified VAS score, WOMAC score, KOOS and MRI measurement of knee articular cartilage integrity by the modified WORMS score. Results: Statistically significant improvement in VAS score, total WOMAC score and total KOOS score was observed from pre injection to 1st follow up at 6 weeks, 2nd follow up at 6 months and final follow up of mean 26.7 months. There was also a significant improvement from 1st follow up to 2nd and final follow up. The modified WORMS score showed a statistically significant decrease of 1.49 %. Conclusion: Intra-articular injection of autologous bone marrow derived culture-expanded MSCs can be considered a potential treatment of early osteoarthritis knee which relieves pain, stiffness, improves physical functions, and improves the articular cartilage integrity.

Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling.

Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate the activity of TGF-β in osteoarthritis progression, we collected knee joints from Dunkin-Hartley (DH) guinea pigs at 3, 6, 9, and 12-month old (n = 8), which develop spontaneous osteoarthritis in a manner extraordinarily similar to humans. Via histology and micro-computed tomography (CT) analysis, we found that the joints exhibited gradual cartilage degeneration, subchondral plate sclerosis, and elevated bone remodeling during aging. The degenerating cartilage showed a progressive switch of the expression of phosphorylated Smad2/3 to Smad1/5/8, suggesting dual roles of TGF-β/Smad signaling during chondrocyte terminal differentiation in osteoarthritis progression. In subchondral bone, we found that the locations and age-related changes of osterix(+) osteoprogenitors were in parallel with active TGF-β, which implied the excessive osteogenesis may link to the activity of TGF-β. Our study, therefore, suggests an association of cartilage degeneration and excessive bone remodeling with altered TGF-β signaling in osteoarthritis progression of DH guinea pigs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:763-770, 2016.

Discussing prognosis with patients with osteoarthritis: a cross-sectional survey in general practice.

Osteoarthritis is a leading cause of chronic pain and disability and one of the most common conditions diagnosed and managed in primary care. Despite the evidence that patients would value discussions about the course of osteoarthritis to help them make informed treatment decisions and plan for the future, little is known of GPs’ practice of, or views regarding, discussing prognosis with these patients. A cross-sectional postal survey asked 2500 randomly selected UK GPs their views on discussing prognosis with patients with osteoarthritis and potential barriers or facilitators to such discussions. They were also asked if prognostic discussions were part of their current practice and what indicators they considered important in assessing the prognosis associated with osteoarthritis. Of 768 respondents (response rate 30.7 %), the majority felt it necessary to discuss prognosis with osteoarthritis patients (n = 738, 96.1 %), but only two thirds reported that it was part of their routine practice (n = 498, 64.8 %). Most respondents found predicting the course of osteoarthritis (n = 703, 91.8 %) and determining the prognosis of patients difficult (n = 589, 76.7 %). Obesity, level of physical disability and pain severity were considered the most important prognostic indicators in osteoarthritis. Although GPs consider prognostic discussions necessary for patients with osteoarthritis, few prioritise these discussions. Lack of time and perceived difficulties in predicting the disease course and determining prognosis for patients with osteoarthritis may be barriers to engaging in prognostic discussions. Further research is required to identify ways to assist GPs making prognostic predictions for patients with osteoarthritis and facilitate engagement in these discussions.

Analysis of distribution and severity of inflammation in patients with osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study

BackgroundIn rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and...

Glycosaminoglycan chemical exchange saturation transfer at 3T MRI in asymptomatic knee joints.

Biochemical alterations such as glycosaminoglycan (GAG) depletion occur early in the course of osteoarthritis, but cannot be detected with standard magnetic resonance techniques. With glycosaminoglycan chemical exchange saturation transfer (gagCEST), a biochemical imaging technique, it is feasible to detect biochemical components in knee joint cartilage. To establish baseline values for gagCEST magnetic resonance imaging (MRI) in knee joint cartilage at 3 Tesla (T). Twenty volunteers (8 women, 12 men; mean age, 24.55 ± 2.35 years;age range, 21-29 years) with no history or clinical findings indicative of knee joint pathologies underwent MRI at 3T. The imaging protocol included three-dimensional (3D) double-echo steady-state sequence for morphological cartilage assessment and a prototype 3D CEST pulse sequence to evaluate the CEST effects in six cartilage regions of the knee joint: (i) lateral femoral condyle; (ii) medial femoral condyle; (iii) lateral tibial plateau; (iv) medial tibial plateau; (v) patella; and (vi) trochlea. We used the asymmetry of the magnetization transfer ratio (MTRasym) parameter to quantify the gagCEST effects in these regions. Regional differences revealed high MTRasym values in the patellar (1.62% ± 1.19%) and the trochlear (1.17% ± 1.29%) cartilages, and low MTRasym values in the medial femoral condyle (0.41% ± 0.58%) and the lateral tibial plateau (0.52% ± 0.53%) cartilages. Regional differences in the gagCEST values must be considered when conducting gagCEST imaging of knee joint cartilage. In the future gagCEST imaging may be an additional feature in the evaluation of the biochemical composition of knee joint cartilage.

The role of ≿ytokines in patients with osteoarthritis and type 2 diabetes mellitus

Purpose: to investigate influence of concentration in plasma tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) on articular syndrome and parameters of carbohydrate metabolism in patients with osteoarthritis (OA) and type 2 diabetes mellitus (T2DM). Methods: The study was performed on 65 patients (29 males), aged 57.9 ± 3.2 with combination OA and T2DM in Regional Hospital of Kharkov. Baseline characteristics of patients included history of OA (7.1 ± 2.3 years), T2DM (8.1 ± 2.5 years). All patients were divided into 2 groups: group 1 (n = 30) – with combined course of OA and T2DM with normal body weight, group 2 (n = 35) – with combined course of OA and T2DM with obesity (BMI≥ 30 kg/m2). The survey plan included: anthropometric data, indices of carbohydrate exchange (insulin, glucose, HbA1C, HOMA-IR) and level of C-reactive protein (CRP). The level of HbA1C was <7.5% in all patients. The level of TNF-α and IL-1β was determined by ELISA. All patients were made X-ray examination of knees. Results: Significant correlation between TNF-α and CRP was determined in 1st group (r=0.59; ⤳<0.05) and 2nd group (r=0.72; ⤳<0.05), also correlation between IL-1β and CRP was determined in 1st group (r=0.61; ⤳<0.05) and 2nd group (r=0.78; ⤳<0.05). Among the 1st group of patients the level of insulin resistance was correlated with TNF-α (r=0.36; ⤳<0.05) and IL-1β (r=0.42; ⤳<0.05). More significant correlation between TNF-α and glucose (r=0.44; ⤳<0.05), HbA1C (r=0.54; ⤳<0.05), insulin resistance (r=0.74; ⤳<0.05), HOMAIR (r=0.63; ⤳<0.05) and between IL-1β and glucose (r=0.42; ⤳<0.05), HbA1C (r=0.40; ⤳<0.05), insulin resistance (r=0.52; ⤳<0.05), HOMAIR (r=0.50; ⤳<0.05) was determined in 2nd group with comorbid pathology and obesity. We noticed, the degree of X-ray changes (by Kellgren-Lawrence) were more in 2nd group in compare with the 1st group. Conclusions: Significant correlation between TNF-α, IL-1β and CRP, glucose, НbА1, insulin resistance, HOMA-IR in group of patients with comorbid pathology and obesity means, that obesity is important factor of pathogenesis relationship immune and metabolic processes in patients with OA and T2DM.

Deformation patterns of cracked articular cartilage under compression

Purpose: It is widely accepted that the mechanical environment surrounding cartilage cells (chondrocytes) has a regulatory role on their metabolism. Very early osteoarthritis (OA) is associated with micro-cracks of the cartilage surface that are thought to alter the mechanical environment of chondrocytes, and hence their metabolism. In this study, we assessed the differences of cartilage deformation patterns between intact and cracked cartilage. Methods: Articular cartilage split line patterns of New Zealand white Rabbits were identified using India-ink. Cracks were made at full thickness of cartilage at 90° to the cartilage surface and oriented perpendicular to the split lines. A controlled load of 2MPa was applied, and stress relaxation observed. Cartilage tissues were then fixed in the compressed state and prepared for histology. Samples were mounted either in plastic and stained with Toluidine blue or mounted in paraffin and stained with Picrosirius red for viewing under a polarized light microscope. Results: The split line patterns of patella, femur, and tibia were found to be consistent. Histological analysis revealed that chondrocyte clusters in the radial zone show compression in the vertical direction and realignment of their vertical long axis to an oblique pattern pointing away from the center of the compression site. Under Linear Polarized Light (LPL), extensive collagen fiber reorientation is apparent as they deform in a combination of crimp and bending (Figure 1). Figure 1, Rabbit tibia mounted in plastic, stained with toluidine blue and viewed under LPL. a, Uncompressed tibia. b, Compressed tibia showing the reoriented collagen fibers (fine blue lines). c, Crack location magnified. Under Circular Polarized Light (CPL), the pattern of collagen fiber reorientation that occurred in the cracked vs. the intact samples is different. There is an upside triangle-shaped zone with the crack representing the center. Collagen fibers at the side of the crack are less reoriented compared to those located farther away, indicating the effect of stress release at the crack edge. The sides of the triangle run at an angle similar to that of the oblique running fibers that are normally present in the radial zone of the cartilage, hence this pattern may emphasize the role of these oblique fibers in supporting compressive loads (Figure 2). Figure 2, Rabbit tibia viewed under CPL. a, Intact compressed tibia cartilage. b, Cracked compressed tibia cartilage highlighting the upside triangle pattern. Conclusions: The combination of crimp and bending of the collagen fibres during deformation may have a protective effect and reduce the amount of deformation transmitted to chondrocytes. The presence of a crack completely changed the deformation patterns in the collagen fibers. This is the first time where the micro-structural architecture and deformation of cracked cartilage under compressive loading has been quantified. The difference in collagen reorientation between intact and cracked samples may provide crucial insight into the load distribution in early OA cartilage that contains cracks, and may help identify how cracked cartilage degenerates. Structural changes in surface zone cartilage are among the earliest signs of very early OA and an understanding of these changes in mechanics and cell signaling may allow for altering the time course of OA by either mechanical or pharmacological intervention.

In vitro and in vivo evaluation of doxycycline-chondroitin sulfate/PCLmicrospheres for intraarticular treatment of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease, which has no complete treatment with medication yet. Intraarticular hyaluronan (HA) injection can decrease pain and modify the natural course of OA. This study was designed to provide long term delivery of an MMP (matrix-metalloproteinase) inhibitor agent-doxycycline, together with matrix regenerative agent-chondroitin sulfate for treating OA which progress with matrix degenerations. Doxycycline (D) and doxycycline-chondroitin sulfate (D-CS) loaded poly-ɛ-caprolactone (PCL) microspheres (MS) were prepared as intraarticular delivery systems. Bio-effectiveness of developed microspheres was first evaluated with three-dimensional in vitro model of OA where both MS showed significant reduction in MMP-13 levels compared to untreated OA-chondrocytes at 15 and 24 days. Significant decrease was observed in GAG release into the media for both D MS and D-CS MS treated groups at 15 and 24 days. Second, the microspheres were injected to rabbit knee in hyaluronan (HA) to evaluate the effectiveness of the treatment. Radiographic scores of D MS and D-CS MS groups improved after 8 weeks when compared to OA group. Mankin-Pitzker histological scores similarly showed improvement with D MS and D-CSMS groups when compared to OA group. Ex vivo hardness tests of cartilages demonstrated superior hardness values with both doses of D-CSMS compared to OA group. D MS showed promising improvement of OA in histology results. Although, both MS groups had similar effects on cells in the in vitro model, D-CSMS had a positive contribution on all in vivo treatment outcomes and showed potential as a new strategy for treatment when applied to OA knee joints.

The course of ultrasonographic abnormalities in knee osteoarthritis: 1 year follow up

Imaging of (peri)articular structures and inflammation with Ultrasonography (US) during the course of osteoarthritis (OA) might contribute to knowledge about early diagnosis of OA, prognosis and possibly the effect of disease modifying drugs. Our goal was to identify the prevalence of distinct patterns (stable vs fluctuating) in a set of US features in a cohort of patients receiving standard multimodal treatment for knee OA at T = 0, T = 3 months and T = 12 months. This was a prospective, explorative study including 55 patients fulfilling the American College of Rheumatology clinical criteria for knee OA. Six US features were investigated including: effusion, synovial proliferation, infrapatellar bursitis, meniscal protrusion, Baker's cyst and cartilage thickness at three time points during 1 year. A composite inflammatory score was composed. Overall prevalence was assessed as well as individual patterns which were appointed as stable or unstable. Inflammation like effusion and synovial hypertrophy does occur in over 40% of patients at some time in the year of follow up and shows a fluctuating pattern. Meniscal protrusion and Baker's cyst however are more stable features. Our study gives insight in the prevalence and course of US abnormalities in patients with knee OA and contributes to the knowledge on the possible role of this imaging modality in research.

Emerging Pathways and Promising Agents with Possible Disease Modifying Effect in Osteoarthritis Treatment

Current modalities for osteoarthritis (OA) treatment are partially safe and effective, and only alleviate the disease symptomatology, but do not modify progression and structural changes of the disease. At present, there is no approved safe and effective disease-modifying OA drug (DMOAD) for clinical application. Therefore, there is an urgent need for discovery of DMOAD in order to treat OA. Hopefully, the new DMOADs would also pave the way for better understanding of OA pathophysiology. Given the fact that there is still no adequate remedy that will modify the course of OA, a number of emerging pathways and promising agents with possible DMOAD effect arise targeting cartilage, synovial membrane, and subchondral bone, or using stem cell therapy, and gene therapy. All these methodologies will be described and discussed in this review. Available treatment methodologies for OA are unsatisfactory. In order to properly treat OA in the future, more realistic option will be the use of multiple drugs, instead of single therapy, which is likely to be ineffective in the treatment of such heterogeneous diseases. Which combination of drugs with DMOAD effect will be suitable for the treatment of OA, remains to be determined in future studies.

Chip is a critical regulator of traf6 degradation and osteoclast formation

Chip is a critical regulator of traf6 degradation and osteoclast formation

T2* mapping for articular cartilage assessment: principles, current applications, and future prospects

With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation-without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented.

Therapeutic Education as Adjuvant Therapy in Rehabilitation of Elderly with Osteoarthritis

Abstract The aim of the study was to assess the effects of an educational program on the course of osteoarthritis in elderly. A number of 40 elderly with osteoarthritis were randomized into two groups: an experimental group and a control group. The experimental group received both pharmacological treatment and the educational program for self-management of the disease, while the other group received only the medical therapy. The evolutivity of the disease was assessed after one year. The experimental group showed a significant improvement of all investigated variables, the evolution of the disease being more favourable compared with the control group (p

Patient reported barriers and facilitators to using a self-management booklet for hip and knee osteoarthritis in primary care: results of a qualitative interview study

BackgroundTo enhance guideline-based non-surgical management of hip or knee osteoarthritis (OA), a multidisciplinary, stepped-care strategy has been implemented in primary care in a region of the Netherlands. To facilitate this implementation, the self-management booklet “Care for Osteoarthritis” was developed and introduced. The aim of the booklet was to educate patients about OA, to enhance the patient’s active role in the treatment course, and to improve the communication with health care providers. To successfully introduce the booklet on a large scale we assessed barriers and facilitators for patients to using this booklet.MethodsSeventeen primary care patients with hip or knee OA who received the self-management booklet participated in this qualitative study using semi-structured interviews. Purposive sampling was used to ensure diversity of the patients’ view about the booklet. The interviews were transcribed verbatim and analysed using a thematic analysis approach.ResultsThree core themes with patient perceived barriers and facilitators to use the booklet emerged from the interviews: 1) the role of health care providers, 2) the patient’s perceptions about OA and its manageability, and 3) the patient’s perceptions about the usefulness of the booklet and patient’s information needs. Regarding the first theme, a barrier was the lack of encouragement from health care providers to use the booklet in the treatment course of OA. Moreover, patients had doubts concerning the health care providers’ endorsement of non-surgical treatment for OA. Barriers from the second theme were: thinking that OA is not treatable or that being pro-active during the treatment course is not important. In contrast, being convinced about the importance of an active participation in the treatment course was a facilitator. Third, patients’ perceptions about the usefulness of the booklet and patients’ information needs were both identified as barriers as well as facilitators for booklet use.ConclusionsThis study contributes to the understanding of patient perceived barriers and facilitators to use a self-management booklet in the treatment course of OA. The results offer practical starting points to tailor the implementation activities of the booklet nationwide and to introduce comparable educational tools in OA primary care or in other chronic diseases.

NFATc1 and NFATc2 repress spontaneous osteoarthritis

Osteoarthritis (OA) was once viewed originally as a mechanical disease of "wear and tear," but advances made during the past two decades suggest that abnormal biomechanics contribute to active dysregulation of chondrocyte biology, leading to catabolism of the cartilage matrix. A number of signaling and transcriptional mechanisms have been studied in relation to the regulation of this catabolic program, but how they specifically regulate the initiation or progression of the disease is poorly understood. Here, we demonstrate that cartilage-specific ablation of Nuclear factor of activated T cells c1 (Nfatc1) in Nfatc2(-/-) mice leads to early onset, aggressive OA affecting multiple joints. This model recapitulates features of human OA, including loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and eventual progression to cartilage effacement and joint instability. Consistent with the notion that NFATC1 is an OA-suppressor gene, NFATC1 expression was significantly down-regulated in paired lesional vs. macroscopically normal cartilage samples from OA patients. The highly penetrant, early onset, and severe nature of this model make it an attractive platform for the preclinical development of treatments to alter the course of OA. Furthermore, these findings indicate that NFATs are key suppressors of OA, and regulating NFATs or their transcriptional targets in chondrocytes may lead to novel disease-modifying OA therapies.

Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part II: Inflammatory background of osteoarthritis.

Osteoarthritis is the most common rheumatoid disease. It may develop as a primary disease of the motor organ or as a secondary one in the course of other inflammatory joint diseases. Similarly to the majority of rheumatoid conditions, the pathogenesis of osteoarthritis has not been fully explained. The fact that its development is determined by adipocytokines, which are inflammatory mediators produced in the adipose tissue, has been known for several years. Additionally, inflammatory processes taking place in the adipose tissue that lead to degenerative changes are the main subject of studies conducted by various immunological laboratories. Degenerative changes in patients with osteoarthritis are frequently accompanied by secondary inflammation with cellular infiltrations in the synovial membrane. In numerous cases, the intensification of inflammatory lesions resembles changes seen in arthritis, particularly in rheumatoid arthritis, which inhibits the differential diagnosis by means of imaging examinations. This may have significant clinical implications, e.g. with respect to sonography, which is the basic imaging examination in diagnosing rheumatoid arthritis, monitoring the efficacy of implemented treatment or confirming remission. This article discusses the pathogenesis of three elements of osteoarthritis, i.e. synovitis (due to the difficulties in differentiation of synovitis in the course of osteoarthritis and in rheumatoid arthritis) as well as osteophytes and subchondral sclerosis (due to the significance of the inflammatory factor in their development).

Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis

ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the development of osteoarthritis (OA), by use of several mouse mutants carrying either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant aggrecan. We have selected recombinant monoclonal antibodies directed against ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017 revealed very high affinity for the enzyme in Biacore analyses and very good specificity in a panel of binding assays. Therefore, we tested CRB0017 in a relevant spontaneous OA model, the STR/ort mouse. STR/ort male mice were recruited at 5 months of age, and treated intra-articularly in each knee with CRB0017 1.2μg, CRB0017 12μg, or vehicle. After 6 weeks, the intra-articular administration of CRB0017 was repeated with the same doses. After 3 months from recruitment, the animals were sacrificed and the femorotibial joints processed for histology and scored in a blind fashion according to both Mankin's and the OARSI methods. All histological scores were significantly decreased in the CRB0017 12μg/knee group compared to vehicle, while administration of CRB0017 1.2μg was associated with a trend to a decrease in the same parameters. Therefore, CRB0017 administered twice in 3 months could modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as assessed histologically. The procedure of blind scoring of the histological samples clearly showed that knee intra-articular administration of CRB0017, an anti-ADAMTS5 antibody, dose-dependently improved disease progression in a relevant animal model of OA.

New treatments for osteoarthritis

To review new data on pharmacologic treatment of osteoarthritis for the years 2011-2012. Duloxetine was approved for the treatment of chronic knee pain due to osteoarthritis and has been conditionally recommended by the American College of Rheumatology. Strontium ranelate was found to significantly decrease the rate of decline in joint space width as well as improve pain scores compared with placebo in a large multicenter study in patients with symptomatic knee osteoarthritis. Nerve growth factor (NGF) monoclonal antibody therapy has shown much promise with regard to improvement in pain; however, clinical development studies were stopped out of concern for adverse events in 2010. After a review by the Food and Drug Administration, this hold may be lifted and further studies may resume in 2013. The biologic agents interleukin-1 receptor antagonist and antitumor necrosis factor antibodies have not been shown to be efficacious nor to alter the course of osteoarthritis. Much research surrounding intra-articular injections of platelet-rich plasma (PRP) has not produced clear evidence that this therapy is efficacious in osteoarthritis. There are presently studies using mesenchymal stem cell therapy for osteoarthritis. Duloxetine, strontium ranelate, and NGF antibodies are promising therapies for symptomatic osteoarthritis. At this time, MSCs and PRP require more investigation.

Expression of Peroxisome Proliferator-activated Receptors α, β, γ, and H- and L-Prostaglandin D Synthase During Osteoarthritis in the Spontaneous Hartley Guinea Pig and Experimental Dog Models

To investigate the expression of peroxisome proliferator-activated receptors (PPAR) α, β, and γ, and hematopoietic and lipocalin-type prostaglandin D synthase (H- and L-PGDS) over the course of osteoarthritis (OA) in the spontaneous Hartley guinea pig and the anterior cruciate ligament transection dog models. Guinea pigs were sacrificed at 2 (control group), 4, 8, and 12 months of age (n = 5 per group). Non-operated (control) and operated dogs were sacrificed at 4, 8, and 12 weeks postsurgery. Cartilage was evaluated histologically using the Osteoarthritis Research Society International (OARSI) guidelines. The expression of PPAR-α, β, γ, and H- and L-PGDS was evaluated by real-time PCR and immunohistochemistry. The nonparametric Spearman test was used for correlation analysis. PPAR-α, β, and γ were detected in medial tibial plateau from control animals in both the spontaneous and surgical models. Levels of PPAR-α and β did not change over the course of OA, whereas PPAR-γ levels decreased during progression of disease. We also observed that the expression of H-PGDS remained unchanged, whereas L-PGDS increased over the course of OA. PPAR-γ levels correlated negatively, whereas L-PGDS levels correlated positively, with the histological score of OA. The level of PPAR-γ decreased, whereas level of L-PGDS increased during the progression of OA. These data suggest that reduced expression of PPAR-γ may contribute to the pathogenesis of OA, whereas enhanced expression of L-PGDS may be part of a reparative process.