Degenerative Cartilage Changes Research Articles

Abnormal Biomechanics at 6 Months Are Associated With Cartilage Degeneration at 3 Years After Anterior Cruciate Ligament Reconstruction

To investigate the changes in landing biomechanics over a 3-year period and their correlation with cartilage degenerative changes in the medial tibiofemoral joint of the knee after anterior cruciate ligament reconstruction (ACLR) using magnetic resonance T1ρ mapping. Thirty-one anterior cruciate ligament-injured patients underwent magnetic resonance imaging of the injured knee before ACLR and 3years after ACLR, as well as biomechanical analysis of a drop-landing task at 6months and 3years after ACLR. Sixteen healthy individuals were recruited and underwent knee magnetic resonance imaging and biomechanical assessment during a drop-landing task. T1ρ cartilage relaxation times were calculated for the medial femur and tibia. ACLR patients exhibited increased peak vertical ground reaction force (VGRF), VGRF impulse, peak knee flexion moment (KFM), and KFM impulse from 6months to 3years (P < .001 for each). Although the ACLR knees showed significantly lower peak VGRF and KFM at 6months (P < .001 for both) when compared with the controls, there were no significant differences at 3years. At 3years, ACLR patients showed higher T1ρ values over the medial femur (P < .001) and tibia (P= .012) when compared with their preoperative values and with healthy control values. Within the ACLR group, side-to-side differences in peak VGRF and sagittal knee biomechanics at 6months were associated with increased T1ρ values from baseline to 3years. The results of this longitudinal study show that landing biomechanics are altered after ACLR but biomechanical abnormalities tend to recover at 3years after ACLR. Differences in lower-extremity mechanics during a landing task at 6months may be associated with cartilage degeneration at 3years after anterior cruciate ligament injury and reconstruction. Level II, prospective trial.

Evaluation of humeral head cartilage using magnetic resonance imaging T1 rho mapping for patients with small-to-medium rotator cuff tears: A pilot study

BackgroundIt is unclear whether smaller rotator cuff tears cause cartilage degeneration. This study was designed to detect early humeral head cartilage degeneration in patients with small-to-medium cuff tears using magnetic-resonance-imaging T1 rho mapping. MethodsFive male and 5 female volunteers without shoulder symptoms (control group) and 5 male and 5 female patients with small-to-medium (<3 cm) rotator cuff tears underwent 3.0-T magnetic resonance imaging of a single shoulder. T1 rho values of the humeral head cartilage were measured and analyzed. ResultsThe total mean T1 rho value was 40.4 ± 3.4 ms for the control group and 45.0 ± 5.3 ms for the patient group. In the control group, the T1 rho values in the inferior articular cartilage were significantly higher than those in the superior and middle articular cartilage. In the patient group, there was no significant difference between all regions. A comparison between the patient and control groups showed that the mean T1 rho values in the superior-to-middle articular cartilage were significantly higher for the patient group than for the control group. However, in the inferior articular cartilage, there was no significant difference between both groups. ConclusionsThis study showed the possibility of early cartilage degenerative changes in the superior-to-middle humeral head articular cartilage of patients with small-to-medium rotator cuff tears.

VEGF-A is associated with early degenerative changes in cartilage and subchondral bone

Paired cartilage and subchondral bone of subjects with no clinical history of joint disorders were analyzed to determine whether antioxidant enzymes, inflammatory cytokines and growth factors can be linked to a pre-osteoarthritis. Tissue explants were phenotyped according to Osteoarthritis Research Society International grading and micro-computed tomography, and also screened for the expression of several markers using quantitative polymerase chain reaction. The expression of these same genes was measured in SW1353 cells treated with hydrogen peroxide, to gain insight into the pathways involved with oxidative stress responses. Vascular endothelial growth factor A (VEGF-A) was up-regulated in the cartilage samples that showed early cartilage or bone degeneration. Oxidative stress in chondrocytes provoked up-regulation of interleukin-1β, interleukin-6, aggrecan, and SRY-box containing gene 9. Our results confirm the hitherto evidence of the deteriorating effects of the oxidative stress on cartilage and suggest the link between VEGF-A and pre-osteoarthritis.

Inhibition of C5a prevents IL-1β-induced alternations in rat synoviocytes in vitro

C5a is an important pro-inflammatory peptide involved in complement activation, membrane attack complex formation, immune cell chemotaxis, and allergic responses. Osteoarthritis is a disease characterized by degenerative changes in articular cartilage. It has recently been found that inflammatory responses play an important role in the pathogenesis of osteoarthritis and also in rheumatoid arthritis, where dysfunctional synoviocytes are involved. We performed a series of studies to verify our hypothesis that inhibition of C5a would prevent IL-1β-induced alternations in rat synoviocytes. In vitro studies were performed with RSC-364 cells to examine the role of C5a in the function of synoviocytes. RSC-364 cells (a rat derived synovial cell line) were treated with IL-1β, IL-1β+siC5a, IL-1β+PMX205 that is antagonist of C5aR, or left untreated. Cell cycle, proliferation, apoptosis, invasion, as well as levels of C5a, IL-17A and TNF-α expression were evaluated. We found that IL-1β could significantly increase the proliferation and invasion capabilities of RSC-364 cells, as well as of C5a IL-17A and TNF-α expression. In contrast, inhibition of C5a by siRNA or application of antagonist of C5aR PMX205 reversed the IL-1β-induced changes in C5a expression, cell cycle, proliferation, apoptosis, invasion, and cytokines releases. Taken together, our study results suggest that IL-1β can increase C5a expression in RSC-364 cells, and that C5a exerts a proinflammatory effect in RSC-364 cells. Inhibition of C5a might represent a new strategy for treating rheumatoid arthritis.

Expression of endoplasmic reticulum stress protein in rabbit condyle cartilage following anterior disk displacement.

Anterior disk displacement (ADD) is a most common subtype of temporomandibular disorders (TMD), which is promoted by chondrocytes apoptosis. However, the signaling pathways that trigger apoptosis are still unknown. The aim of this study was to investigate the expression of endoplasmic reticulum (ER) stress-related proteins in the condylar cartilage of rabbits following ADD. Sixty healthy adult rabbits were randomly assigned to the experimental and sham-operated control groups (n=12). The experimental rabbits were subjected to surgical ADD in the right temporomandibular joints. The production of ER stress-related proteins C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), cleaved caspase-3, and caspase-12 in cartilage was evaluated by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. Our results showed that the expression of CHOP, GRP78, cleaved caspase-3, and caspase-12 increased significantly along with degenerative changes in cartilage after ADD. These results indicate that the ER stress pathway is activated in ADD cartilage and might promote the development of TMD.

Effects of dietary saturated fatty acid consumption on cartilage health and trauma-induced osteoarthritis in rats

Purpose: Experimental studies show that administering diets rich in lipids (high fat diets) leads to osteoarthritis (OA). Thus, it appears from the available literature that the source, or type of dietary fat and its level of saturation may be a critical factor in the development of an underlying inflammatory condition in the body that may lead to OA development. There are different types of saturated fatty acids. Western diet predominantly consist of fats rich in stearic acid, palmitic acid, myristic acid and lauric acid. However, so far no studies have investigated what type of saturated fatty acid in particular lead to cartilage damage. Therefore the goal of this present study is to evaluate the effects of administering different types of saturated diets on the morphology of the cartilage, subchondral bone and pain related behavior. Methods: The current study evaluates the chronic impact of high saturated fat feeding on joint cartilage health using a rat model. Male wistar rats weighing 330–340g received either corn starch diet or a diet rich in simple sugars including fructose together with either lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18) or beef tallow (mainly stearic and trans fatty acids). After 16 weeks, knee OA was assessed by cartilage and synovium histology in addition to bone morphology. Serum cytokine concentrations were determined with multiplex assay. We further monitored lipid profile, glucose levels, and body weight and food consumption throughout the study period. Furthermore, the influence of different saturated fatty acid (SFA) types on the progression of OA was evaluated in menisectomy OA model by monitoring pain-related behavior, the changes in glial activity in the spinal cord (SC) and the dorsal root ganglions (DRG) of rats fed with the different saturated fat diets. Results: Our results indicate that the rats on a high-carbohydrate diet, stearic acid rich and plamitic acid diet showed cartilage degenerative changes that are similar to OA cartilage. Surprisingly, the rats that were fed with lauric acid and myristic acid saturated fats showed similar cartilage structure to control rats that were fed with corn starch diet, indicating marked differences in OA risk depending on the type of dietary fatty acids. As cartilage changes progress, we found that supplementation with stearic acid and palmitic acid markedly increased glucose intolerance, abdominal obesity, hypertension and fatty liver. However such effects were decreased in the rats that are fed with lauric and myristic acid fats. Furthermore, the rats on palmitic (PA) and stearic acid (SA) diets increased the progression of OA in menisectomy rats, which was characterized by increased knee cartilage degeneration and decreased bone volume density (BMD). In addition, these diet groups also exhibited decreased hind paw withdrawal thresholds, grip strength, and increased joint hypersensitivity compared to the other saturated fat groups. Furthermore, significant spinal astrogliosis and microgliosis were also observed in these diet groups. On the contrary, lauric acid (LA) diet group rats exhibited decreased degeneration of the cartilage, increased hind paw withdrawal thresholds, grip strength and decreased joint hypersensitivity. In addition, lower number of spinal GFAP and IBA-1 positive cells were observed signifying decreased astrogliosis and microgliosis respectively. Conclusions: In conclusion, our study indicates that effect of saturated fats on OA risk and pain depends on the kind of fatty acids present in the blood. Thus, reducing or modulating certain types of saturated fatty acids in the diet may help in preventing or slowing the progression of OA.

Loss of Wnt9a and Wnt4 causes degenerative joint alterations

Purpose: Both induced and reduced Wnt-signaling has been shown in literature to contribute to osteoarthritis. The Wnt-ligands Wnt9a and Wnt4 are of special interest since they are expressed in cells of the joint forming region and are positive regulators of chondrocyte maturation. More specifically, Wnt9a regulates the pace of chondrocyte proliferation and maturation, while Wnt4 regulates chondrocyte maturation at the transition from prehypertrophic to hypertrophic chondrocytes and misexpression accelerates chondrocyte maturation. Wnt9a downregulation has been shown in OA patients, and knockout or inhibition of β-catenin leads to the destruction of articular cartilage in mice. In addition, Wnt-antagonists Dkk-1 and Frzb-1 are expressed by articular chondrocytes, suggesting that canonical Wnt-signaling in articular chondrocytes has to be tightly controlled. Methods: Here, we investigate the effects of loss of Wnt9a and the combined loss of Wnt9a and Wnt4 with respect to joint maintenance in aged mice. To circumvent the postnatal lethality of loss of Wnt9a and Wnt4, the genes for both Wnt ligands were either conditionally deleted in the limb mesenchyme (Prx1-Cre), or in the case of Wnt9a in the superficial zone of the articular cartilage (Prg4-Cre). The resulting skeletal phenotype was analyzed at the ages of 6, 9 and 12 months by μCT and histology. To investigate expression changes in chondrocytes and synovial fibroblasts upon deletion of Wnt9a and Wnt4, we isolated superficial zone cells and deeper layered chondrocytes from femoral condyles and tibial plateaus of the knee and synovial fibroblasts from paws of 8-day-old Wnt9afl/fl and Wnt4fl/fl mice. Cultured cells were either infected with a lentivirus expressing or non-expressing Cre and alterations in gene expression levels were measured via qPCR. Results: The limb specific Wnt9a knockout mice show a joint phenotype at the age of 9 months. The onset of the phenotypic changes in the joints is accelerated by the additional loss of Wnt4. Phenotypically, the articular cartilage shows loss of proteoglycans, erosion, reduction of subchondral cortical thickness, and formation of ectopic calcifications and osteophytes at the knee joint. These alterations are progressively worsening with the age of the mice. Concomitant with the reduction of subchondral cortical thickness, an enriched TRAP-positive cell population can be found in the subchondral compartment. Mice with a conditional loss of Wnt9a in the superficial articular zone show degenerative changes of the articular cartilage at an age of 12 months. In the in vitro chondrocyte culture experiments a downregulation of Prg4 and an upregulation of Tnfsf11 (encoding RANKL) was observed upon the combined knockdown of Wnt9a and Wnt4 while an upregulation of Il-6 was noted upon deletion of Wnt9a alone. In fibroblast cultures an upregulation of Cd34 and metalloproteases Mmp9, Adamts-4 and Adamts-5 and can be detected in Wnt9a single and combined Wnt9a and Wnt4 knowdowns. Conclusions: Taken together, our results further support the notion that imbalanced Wnt-signaling can cause degenerative joint alterations. Furthermore, we show that Wnt9a and Wnt4 signaling are critical for maintenance of the joint. Yet, the underlying mechanisms remain to be elucidated in the future.

Proteoglycan density of the talar articular cartilage is reduced in those with chronic ankle instability

Purpose: Clear links have been made between both lateral ankle sprains and chronic ankle instability (CAI) and the development of ankle post-traumatic osteoarthritis (PTOA). Current visualization techniques such as arthroscopy and standard MRI are ineffective at quantifying early degenerative changes to the talar articular cartilage. The most promising approaches for slowing ankle PTOA progression include early conservative interventions to restore appropriate joint biomechanics. Thus, identifying visualization techniques sensitive to early degenerative changes of the talar articular cartilage is needed. Therefore, the purpose of this investigation is to determine if CAI patients have lower proteoglycan density in their talar cartilage compared to uninjured controls as measured by T1ρ MRI. Methods: Fifteen CAI (age: 21.2 ± 1.8 years, height: 1.7 ± .8 m, mass: 67.0 ± 7.7 kg) and fifteen controls (age: 21.0 ± 2.5 years, height: 1.7 ± .8 m, weight: 69.6 ± 13.2 kg) volunteered to participate. CAI inclusion criteria were in accordance with the International Ankle Consortium guidelines. Relative to the controls, CAI participants had a history of multiple lateral ankle sprains (4.0 ± 2.1 vs. 0.0 ± 0.0 sprains), multiple giving way episodes within the past 6 months (6.6 ± 5.1 vs. 0.0 ± 0.0 episodes), higher Identification of Functional Ankle Instability scores (22.9 ± 2.8 vs. 0.1 ± 0.5), and greater limitations in self-reported function based on the Foot and Ankle Ability Measure (85.9 ± 9.7% vs. 100.0 ± 0.0%) and Foot and Ankle Ability Measure Sport (68.4 ± 20.6% vs. 100.0 ± 0.0%). Proteoglycan density was assessed using T1ρ MRI with greater T1ρ relaxation times interpreted as reduced proteoglycan density. A Siemens Magnetom TIM Trio 3T scanner and an 8-channel flex coil in conjunction with three-dimensional Fast Low Angle Shot (FLASH) with a spin lock power at 500 Hz, five different spin lock durations (40, 30, 20,10, 0 ms) was used to acquire the T1ρ MRI. Participants were non-weight bearing for 30 minutes prior to the scan to unload the cartilage. Voxel by voxel T1rho relaxation times were calculated from a five image sequence created with a MatLab program. Segmentation of the T1ρ talar cartilage was performed manually using ITK-SNAP software. Four regions of interest: anteromeidal, anterolateral, posteromedial, and posterolateral were identified during segmentation. Mean T1ρ relaxation times in each region of interest were compared between CAI patients and healthy controls using independent sample t-tests and an a priori alpha level of 0.05. Results: The CAI and controls groups were similar in terms of their age, height, and mass (P ≥ 0.433). Measures of injury history and self-reported function differed between the groups (P < 0.001) as expected. CAI patients had significantly higher T1ρ relaxation times in three of the four regions of interest including the anterolateral region (CAI: 66.57 ± 11.42 ms, Control: 57.73 ± 5.91 ms, P = 0.013), posteromedial region (CAI: 63.48 ± 12.43 ms, Control: 54.71 ± 10.84 ms, P = 0.049), and posterolateral region (CAI: 65.97 ± 11.75 ms, Control: 54.20 ± 10.03 ms, P = 0.006). No differences were noted in the anteromedial region (CAI: 67.61 ± 13.30 ms, Control: 60.91 ± 13.65 ms, P = 0.184). Conclusions: CAI patients showed higher T1ρ relaxation times compared to controls in three of the four regions of interest suggesting reduced proteoglycan density in the talar cartilage. This finding supports the existing arthroscopic literature that illustrates early degenerative changes in CAI patients. Further research is needed to determine the underlying mechanisms of these degenerative changes and to identify therapeutic interventions capable of slowing the progression of these degenerative changes following lateral ankle sprains and CAI.

COMPARISON OF THE DIAGNOSTIC ACCURACY OF MAGNETIC RESONANCE IMAGING AND ULTRASOUND EXAMINATION FOR X-RAY NEGATIVE STAGE OF KNEE JOINTS OSTEOARTHRITIS

Purpose. To compare of the diagnostic accuracy of ultrasonography (US) with magnetic resonance imaging (MRI) as a reference in the assessment of pathological changes of the soft tissues at the X-ray negative stage of knee joint osteoarthritis (OA). Materials and methods. Nineteen patients with X-ray negative stage of knee OA diagnosed in 2015 underwent US and MRI of the knee joints. We estimated the sensitivity and specificity, positive and negative predictive values for pathological changes in 7 distinct anatomical areas on US comparing to MRI. Results. There were no false positive results. The findings of US and MRI coincided for the presence of an excess amount of free fluid in the joint cavity and suprapatellar bursa synovitis and the presence of Baker’s cyst, 15 (79%) and 4 (21%) patients, respectively. More o‡ en, false-negative results on US have been seen in assessing changes in the lateral meniscus and osteophytes: 2 (11%) diagnosed cases vs 15 (79%) for MRI, respectively. The degenerative changes in the medial meniscus were found in 10 (52.6%) on US compared to 15 (79%) for MRI, respectively. Method of US showed the low sensitivity in the detection of early pathological changes of the knee ligaments: sensitivity and predictive value of negative results accounted for the cruciate were 47% and 18%, for collateral ones only 24% and 13%, respectively. Conclusion. Ultrasound examination is highly effective in the diagnosis of synovitis, free fluid in the joint cavity and suprapatellar bursa and Baker’s cysts in patients with X-ray negative stage of knee OA. It helps to identify the group of patients with the highest risk of progression of OA. The method of ultrasound is significantly inferior to MRI in the diagnosis of early degenerative changes in ligaments, the menisci and cartilage of the joint.

Tibial Osteotomy as a Mechanical Model of Primary Osteoarthritis in Rats

This study has presented the first purely biomechanical surgical model of osteoarthritis (OA) in rats, which could be more representative of the human primary disease than intra-articular techniques published previously. A surgical tibial osteotomy (TO) was used to induce degenerative cartilage changes in the medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the medial knee compartment of the operated animals was evaluated histologically and through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX-II). In-vivo biomechanical analyses were carried out using a musculoskeletal model of the rat hindlimb to evaluate the loading conditions in the knee pre and post-surgically. Qualitative and quantitative medial cartilage degeneration consistent with OA was found in the knees of the operated animals alongside elevated CTX-II levels and increased tibial compressive loading. The potential avoidance of joint inflammation post-surgically, the maintenance of internal joint biomechanics and the ability to quantify the alterations in joint loading should make this model of OA a better candidate for modeling primary forms of the disease in humans.

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent

BackgroundArticular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent.MethodsWe induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T2-calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation.ResultsSignificant differences in the SIR and T2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA.ConclusionWe evaluated the SIR and T2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone.

The striking predilection of temporomandibular disorders (TMD) in women, especially during gonad-intact puberty or reproductive years, indicates that oestrogen plays an important role in the progression of TMD, but the underlying mechanism remains unclear. In this study, unilateral anterior crossbite (UAC) was used to create temporomandibular joint osteoarthritis (TMJ OA) models in rats, while 17β-estradiol (E2) injections were applied to mimic patients with high-physiological levels of oestrogen. Micro-CT scanning, histological staining and real-time PCR assays were preformed to observe the degenerative changes in the mandibular condylar cartilage and subchondral bone. The results showed that obvious degradation was found in the condylar cartilage and subchondral bone of rats with UAC procedure, including decreased cartilage thickness, loss of extracellular matrix, increased apoptotic chondrocytes and expression of pro-inflammatory and catabolic factors, decreased bone mineral density and increased osteoclast activity. E2 supplements aggravated the condylar cartilage degradation but reversed the abnormal bone resorption in the subchondral bone induced by UAC. Our results revealed that high-physiological oestrogen plays a destructive role in condylar cartilage but a protective role in subchondral bone at the early stage of TMJ OA. These dual and distinct effects should be given serious consideration in future OA treatments.

Recent advances in articular cartilage evaluation using computed tomography and magnetic resonance imaging.

Articular cartilage is a critical joint tissue and its evaluation remains a diagnostic challenge in horses. Coupled with a poor capacity for healing, early degenerative changes in articular cartilage are difficult to characterise using routine diagnostic imaging evaluations. Both computed tomography (CT) and magnetic resonance imaging (MRI) provide volumetric joint assessment and highlight morphological and quantitative properties of articular cartilage, improving assessment of this essential tissue. While the use of CT and MRI for joint evaluation is not new, there still remains a shortage of literature and scientific studies on the ability of these methods to evaluate articular cartilage in the horse. This review article summarises current CT and MRI techniques capable of characterising equine articular cartilage, highlights recent advances in these techniques and discusses the numerous methods studied in human subjects that have been minimally investigated in horses. Imaging techniques are presented in terms of their capabilities of offering morphological and quantitative evaluation along with a discussion of their benefits and limitations. Finally, it summarises the current state-of-the-art approaches and identifies unmet clinical imaging needs to propel the advancement of articular cartilage and joint imaging in the horse.

Potential pharmaceutic effect of Shilajit (mumie) on experimental osteoarthritis in rat

Osteoarthritis (OA) is a worldwide joint disease with clinically loss of motion and pain in human. The conventional treatments are associated with essential side effects. In folk medicine, Shilajit is applied for treatment of arthritis and bone fractures. The present study evaluated effect of Shilajit on the osteoarthritis in rat model. Thirty-six adult male rats were randomly divided into two groups including OA and treated with Shilajit groups. OA was induced by injection of monosodium iodoacetate in the articular space of femorotibial joint. Aqueous extract of Shilajit was given to the treatment group by gavage as daily during experimental course until 21 days. The joint samples were investigated 7, 14, and 21 days post induction. The main macroscopic changes in the affected joints were swelling and congestion at early stages. Histopathologic study showed surface irregularity, erosion and fissures, necrotic chondrocytes, depletion of toluidine blue staining, and lysis of subchondral bone in both OA and Shilajit groups after 7 and 14 days. Synovium revealed synovial cells hyperplasia and inflammatory cells infiltration. Moderate to advanced OA was seen in both groups without significant difference. After 21 days, histopathologic scores of destructive damages and synovitis were reduced in the Shilajit group and showed significant difference in compare to OA group. The present study shows that aqueous extract of Shilajit decreased cartilage degenerative changes in knee osteoarthritis. Also, it reduced inflammatory reactions in synovial membrane.

Three-dimensional visualization and pathologic characteristics of cartilage and subchondral bone changes in the lumbar facet joint of an ovariectomized mouse model

Background ContextLow back pain (LBP) is more prevalent among postmenopausal women than men. Ovariectomy (OVX) is an established animal model that mimics the estrogen deficiency of postmenopausal women. Little is known about the three-dimensional (3D) morphologic properties of cartilage and subchondral bone changes in the lumbar facet joint (LFJ) of an OVX mouse model. PurposeThe purpose of this study was to characterize the 3D morphologic change of cartilage and subchondral bone in the LFJ of an OVX mouse model. Study DesignThree-dimensional visualization and a histologic study on degenerative changes in cartilage and subchondral bone in the LFJ of an OVX mouse model were conducted. Materials and MethodsOvariectomy is performed to mimic postmenopausal changes in adult female mice. We present an imaging tool for 3D visualization of the pathologic characteristics of cartilage and subchondral bone changes LFJ degradation using propagation-based phase-contrast computed tomography (PPCT). The samples were further dissected, fixed, and stained for histologic examination. ResultsPropagation-based phase-contrast computed tomography imaging provides a 3D visualization of altered cartilage with a simultaneous high detail of the subchondral bone abnormalities in an OVX LFJ model. A quantitative analysis demonstrated that the cartilage volume, the surface area, and thickness were decreased in the OVX group compared with the control group (p<.05). Meanwhile, these decreases were accompanied by an obvious destruction of the subchondral bone surface and a loss of trabecular bone in the OVX group (p<.05). The delineation of the 3D pathologic changes in the PPCT imaging was confirmed by a histopathologic method with Safranin-O staining. Tartrate-resistant acid phosphatase staining revealed an increased number of osteoclasts in the subchondral bone of the OVX mice compared with that of the control group. ConclusionsThese results demonstrated that a mouse model of OVX-induced LFJ osteoarthritis (OA)-like changes was successfully established and showed a good resemblance to the human OA pathology. Propagation-based phase-contrast computed tomography has great potential to becomea powerful 3D imaging method to comprehensively characterize LFJ OA and to effectively monitor therapeutics. Moreover, degenerative LFJ possesses a severe morphologic change in the subchondral bone, may be the source of postmenopausal LBP, and has the potential to be a novel therapeutic target for LBP treatment.

Diagnosis and Treatment of Arthritis

Changes in the musculoskeletal system due to aging lead to muscle weakness, muscle atrophy, degenerative changes in joints and cartilage, and decreased bone density. Pain in the joints is a very common and subjective symptom. There are various causes, such as referred pain or neurological pain that make it difficult to diagnose correctly. Especially, in elderly patients, their detailed history and a physical examination are important for the diagnosis of arthritis, and consideration of the effects of underlying diseases and drugs is essential. In this review, we first describe the clinical approach to diagnosis of arthritis, and briefly describe the diagnosis and treatment of osteoarthritis, rheumatoid arthritis, and gout, which are common arthritis causing gait disorders in the elderly. Key Words: Rheumatoid arthritis, Osteoarthritis, Gout, Diagnosis, Treatment

High-Frequency Ultrasound Imaging of Tidemark In Vitro in Advanced Knee Osteoarthritis

High-frequency ultrasound imaging has been widely adopted for assessment of the degenerative changes of articular cartilage in osteoarthritis (OA). Yet, there are few reports on investigating its capability to evaluate subchondral bone. Here, we employed high-frequency ultrasound imaging (25 MHz) to examine in vitro the tidemark in cylindrical osteochondral disks (n = 33) harvested from advanced OA knees of humans. We found good correspondence in morphology observed by ultrasound imaging and micro-computed tomography. Ultrasound roughness index (URI) of tidemark was derived from the raw radiofrequency signals to compare with bone quality factors, including bone volume fraction (BV/TV) and bone mineral density (BMD) measured by micro-computed tomography, using the Spearman correlation (ρ). URI of the tidemark was negatively associated with the subchondral plate BV/TV (ρ = −0.73, p < 0.001), BMD (ρ = −0.40, p = 0.020), as well as the underneath trabecular bone BV/TV (ρ = −0.39, p = 0.025) and BMD (ρ = −0.43, p = 0.012). In conclusion, this preliminary study demonstrated that morphology measured by high-frequency ultrasound imaging could reflect the quality of the subchondral bone. High-frequency ultrasound is a promising imaging tool to evaluate the changes of the subchondral bone in addition to those of the overlying cartilage in OA.

Monitoring osteoarthritis progression using near infrared (NIR) spectroscopy

We demonstrate in this study the potential of near infrared (NIR) spectroscopy as a tool for monitoring progression of cartilage degeneration in an animal model. Osteoarthritic degeneration was artificially induced in one joint in laboratory rats, and the animals were sacrificed at four time points: 1, 2, 4, and 6 weeks (3 animals/week). NIR spectra were acquired from both (injured and intact) knees. Subsequently, the joint samples were subjected to histological evaluation and glycosaminoglycan (GAG) content analysis, to assess disease severity based on the Mankin scoring system and to determine proteoglycan loss, respectively. Multivariate spectral techniques were then employed for classification (principal component analysis and support vector machines) and prediction (partial least squares regression) of the samples’ Mankin scores and GAG content from their NIR spectra. Our results demonstrate that NIR spectroscopy is sensitive to degenerative changes in articular cartilage, and is capable of distinguishing between mild (weeks 1&2; Mankin <=2) and advanced (weeks 4&6; Mankin =>3) cartilage degeneration. In addition, the spectral data contains information that enables estimation of the tissue’s Mankin score (error = 12.6%, R2 = 86.2%) and GAG content (error = 7.6%, R2 = 95%). We conclude that NIR spectroscopy is a viable tool for assessing cartilage degeneration post-injury, such as, post-traumatic osteoarthritis.

Orientation anisotropy of quantitative MRI relaxation parameters in ordered tissue

In highly organized tissues, such as cartilage, tendons and white matter, several quantitative MRI parameters exhibit dependence on the orientation of the tissue constituents with respect to the main imaging magnetic field (B0). In this study, we investigated the dependence of multiple relaxation parameters on the orientation of articular cartilage specimens in the B0. Bovine patellar cartilage-bone samples (n = 4) were investigated ex vivo at 9.4 Tesla at seven different orientations, and the MRI results were compared with polarized light microscopy findings on specimen structure. Dependences of T2 and continuous wave (CW)-T1ρ relaxation times on cartilage orientation were confirmed. T2 (and T2*) had the highest sensitivity to orientation, followed by TRAFF2 and adiabatic T2ρ. The highest dependence was seen in the highly organized deep cartilage and the smallest in the least organized transitional layer. Increasing spin-lock amplitude decreased the orientation dependence of CW-T1ρ. T1 was found practically orientation-independent and was closely followed by adiabatic T1ρ. The results suggest that T1 and adiabatic T1ρ should be preferred for orientation-independent quantitative assessment of organized tissues such as articular cartilage. On the other hand, based on the literature, parameters with higher orientation anisotropy appear to be more sensitive to degenerative changes in cartilage.

Compromised autophagy precedes meniscus degeneration and cartilage damage in mice.

Autophagy is a cellular homeostasis mechanism that facilitates normal cell function and survival. Objectives of this study were to determine associations between autophagic responses with meniscus injury, joint aging, and osteoarthritis (OA), and to establish the temporal relationship with structural changes in menisci and cartilage. Constitutive activation of autophagy during aging was measured in GFP-LC3 transgenic reporter mice between 6 and 30 months. Meniscus injury was created by surgically destabilizing the medial meniscus (DMM) to induce posttraumatic OA in C57BL/6J mice. Levels of autophagy proteins and activation were analyzed by confocal microscopy and immunohistochemistry. Associated histopathological changes, such as cellularity, matrix staining, and structural damage, were graded in the meniscus and compared to changes in articular cartilage. In C57BL/6J mice, basal autophagy was lower in the meniscus than in articular cartilage. With increasing age, expression of the autophagy proteins ATG5 and LC3 was significantly reduced by 24 months. Age-related changes included abnormal Safranin-O staining and reduced cellularity, which preceded structural damage in the meniscus and articular cartilage. In mice with DMM, autophagy was induced in the meniscus while it was suppressed in cartilage. Articular cartilage exhibited the most profound changes in autophagy and structure that preceded meniscus degeneration. Systemic administration of rapamycin to mice with DMM induced autophagy activation in cartilage and reduced degenerative changes in both meniscus and cartilage. Autophagy is significantly affected in the meniscus during aging and injury and precedes structural damage. Maintenance of autophagic activity appears critical for meniscus and cartilage integrity.