Degenerative Cartilage Changes Research Articles

Preliminary Exploration of T1ρ and T2 Mapping in Porcine Articular Cartilage Using Very-Low-Field Magnetic Resonance Imaging.

The high prevalence of osteoarthritis emphasizes the need for a cost-effective and accessible method for its early diagnosis. Recently, the portability and affordability of very-low-field (VLF) magnetic resonance imaging (MRI, 10-100 mT) have caused it to gain popularity. Nevertheless, there is insufficient evidence to quantify early degenerative changes in cartilage using VLF MRI. This study assessed the potential of T1ρ and T2 mapping for detecting degenerative changes in porcine cartilage specimens using a 50 mT MRI scanner. T2- and T1ρ-weighted images were acquired using a 50 mT MRI scanner with 2D spin-echo and triple-refocused T1ρ preparation sequences. MRI scans of porcine cartilage were also acquired using a 3 T MRI scanner for comparison. A mono-exponential algorithm was applied to fit a series of T2- and T1ρ-weighted images. T2 values for CuSO4·5H2O solutions measured via Carr-Purcell-Meiboom-Gill (CPMG) and spin-echo sequences were compared to verify the algorithm's reliability. The nonparametric Kruskal-Wallis statistical test was used to compare T2 and T1ρ values. Experimental repeatability was assessed using the root-mean-square of the coefficient of variation (rmsCV). T2 values of the CuSO4·5H2O solutions obtained using the spin-echo sequence showed differences within 2.3% of those obtained using the CPMG sequence, indicating the algorithm's reliability. The T1ρ values for varying concentrations of agarose gel solutions were higher than the T2 values. Furthermore, 50 mT and 3 T MRI results showed that both the T1ρ and T2 values were significantly higher for porcine cartilage degraded for 6 h vs intact cartilage, with p-values of 0.006 and 0.01, respectively. Our experimental results showed good reproducibility (rmsCV < 8%). We demonstrated the feasibility of quantitative cartilage imaging via T2 and T1ρ mapping at 50 mT MRI for the first time.

Clinical and radiological outcome of acute quadriceps tendon repair at 2 - year follow-up.

Though previous studies on surgical quadriceps tendon repair reported good to satisfactory results its impact on knee extensor strength and patellofemoral joint is unknown. The purpose of the study was to assess the clinical and functional outcome by quantifying subjective knee related outcome, isokinetic extensor strength complemented by magnetic resonance imaging (MRI). For this retrospective clinical trial twenty-one patients with a mean age of 59.1 (±14.9) years were carried out for follow-up evaluation. For clinical outcome numeric rating scale for pain (NRS), Kujala anterior knee pain score, Knee osteoarthritis outcome score (KOOS) with its subscores, Tegener Activity Score (TAS), Isokinetic extensor strength testing (ISO) and the Limb symmetry index (LSI) were utilized. Muscle volume (Vmqf), atrophy and cartilage status were assessed on MRI. Tendon integrity and implant loosening were evaluated. Statistical analysis was carried out using Student´s t-test, Pearson and Spearman correlation coefficient. Mean follow-up was 56.2 (± 17.5) months. Clinical outcomes in mean were as follows: NRS 1.7 (±2.0), Kujala score 75.8 (± 15.8) points; KOOS 62.9 (±30.6) % (Subscores: (KOOSPain 84 (± 18.3)%, KOOSSymptoms 63.4 (± 15.3) %, KOOSADL 79.8% (± 19.4)%, KOOSSports&Rec 61.5 (± 28.8))%, TAS 3.7 (± 1.2). Mean ISO difference was 3.7 (±32.3) %). 41.2% of patients had an LSI < 90% and showed non-significantly (p > 0.05) better outcomes in NRS, Kujala score and KOOS than patients with LSI < 90%. ISO correlated with better subjective outcome (r > 0.5) but not with MRI findings. Vmqf asymmetry > 10% was seen in 41,2% of patients. Degenerative muscle and cartilage changes were few and low grade. One tendon showed partial retear. Patients showed no signs of implant loosening. Distal quadriceps tendon repair leads to satisfactory subjective outcome in patients with low to moderate activity levels. Tendon integrity was reliably restored. However, extensor strength deficits remain in more than 40% of patients. Atrophy signs of advanced fatty infiltration were recorded in 15% and patellofemoral cartilage defects in 20% of all patients, indicating that previous assessment tools do not display functional outcome adequately.

New insights into the mechanisms and therapeutic strategies of chondrocyte autophagy in osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. KEY MESSAGES: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis.

A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.

Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.

Efficacy of adipose—derived stromal vascular fraction in treatment of osteoarthritis: an experimental study

BackgroundOsteoarthritis OA is a common progressive disabling disease. Current research aims at finding therapies to prevent its progression. In this work, we assessed the therapeutic role of intra-articular injection of stromal vascular fraction SVF in collagenase induced knee OA in rats.ResultsPost right Knee OA induction in 42 Wistar rats, histopathological examination and quantification of articular cartilage degeneration using Mankin’s score revealed degenerative changes were significantly higher in untreated Group II compared to SVF treated Group III at 1 month (10.75 ± 0.50 and 2.50 ± 0.53, P = 0.001) and 2 months (8.50 ± 0.58, 0.50 ± 0.53, P = 0.001), respectively. Morphometric computerized image analysis revealed a significant difference between treated, untreated and healthy control group I regarding chondrocyte cellular count, articular cartilage thickness and optical density OD of the cartilage (P < 0.001). Group II contained the least chondrocyte cellular count. Also, articular cartilage thickness at 2 months was significantly less in Group II compared to SVF treated group (P < 0.001). The OD in Safranin-stained slides, as an indicator of proteoglycan content of the matrix, was highest in Group I followed by Group III and lowest in Group II with a highly significant difference between untreated and treated groups at 1 month (67.32 ± 4.25, 81.77 ± 3.09, P = 0.000) and 2 months (71.60 ± 3.49, 83.26 ± 5.47, P = 0.000), respectively.ConclusionTreatment with adipose-derived SVF decreased the development of articular cartilage degenerative changes at early stages of induced OA in rats. Later, on follow-up, the preserved articular cartilage thickness, cellular count and increased proteoglycan content rendered SVF a promising regenerative therapy for Knee OA.

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja

BackgroundPatellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks.MethodsPatella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT).ResultsOur results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone.ConclusionThe early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.

Osteoarthritis (OA) is characterized by articular cartilage erosion, pathological subchondral bone changes, and signs of synovial inflammation and pain. We previously identified p[63-82], a bone morphogenetic protein 7 (BMP7)-derived bioactive peptide that attenuates structural cartilage degeneration in the rat medial meniscal tear-model for posttraumatic OA. This study aimed to evaluate the cartilage erosion-attenuating activity of p[63-82] in a different preclinical model for OA (anterior cruciate ligament transection-partial medial meniscectomy [anterior cruciate ligament transection (ACLT)-pMMx]). The disease-modifying action of the p[63-82] was followed-up in this model for 5 and 10 weeks. Skeletally mature male Lewis rats underwent ACLT-pMMx surgery. Rats received weekly intra-articular injections with either saline or 500 ng p[63-82]. Five and 10 weeks postsurgery, rats were sacrificed, and subchondral bone characteristics were determined using microcomputed tomography (µCT). Histopathological evaluation of cartilage degradation and Osteoarthritis Research Society International (OARSI)-scoring was performed following Safranin-O/Fast Green staining. Pain-related behavior was measured by incapacitance testing and footprint analysis. Histopathological evaluation at 5 and 10 weeks postsurgery showed reduced cartilage degeneration and a significantly reduced OARSI score, whereas no significant changes in subchondral bone characteristics were found in the p[63-82]-treated rats compared to the saline-treated rats. ACLT-pMMx-induced imbalance of static weightbearing capacity in the p[63-82] group was significantly improved compared to the saline-treated rats at weeks 5 postsurgery. Footprint analysis scores in the p[63-82]-treated rats demonstrated improvement at week 10 postsurgery. Weekly intra-articular injections of p[63-82] in the rat ACLT-pMMx posttraumatic OA model resulted in reduced degenerative cartilage changes and induced functional improvement in static weightbearing capacity during follow-up.

CHONDROCYTE-SPECIFIC KNOCKOUT OF PIEZO ION CHANNELS PROTECTS AGAINST POST-TRAUMATIC OSTEOARTHRITIS

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CREERT2;Piezo1fl/flPiezo2fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.

Inotodiol ameliorates the progression of osteoarthritis: An in vitro and in vivo study

AbstractOsteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.

Age-Related Gene and Protein Expression in Mouse Mandibular Condyle Analyzed by Cap Analysis of Gene Expression and Immunohistochemistry

Introduction: Aging, an inevitable physiological process, leads to morphological and histological degenerative changes in the mandibular condylar cartilage (MCC); however, the molecular mechanism has not yet been elucidated, and little information is available on age-related factors. Therefore, this study was designed to identify age-related factors by investigating the age-related differentially expressed genes (DEGs) and localization of their translated protein expression in the mandibular condyle. Methods: Mandibular condyles were collected from 10- and 50-week-old mice. Total RNA was extracted from the samples and then analyzed using cap analysis of gene expression (CAGE) to identify age-related DEGs. Gene ontology (GO) enrichment analysis was performed to determine which biological processes were most affected by aging in terms of gene expression using Metascape. The mandibular condyle samples were processed for histology to investigate morphological changes caused by aging and for immunohistochemistry to localize the protein expression encoded by age-related genes identified with CAGE. Semi-quantitative immunohistochemistry was performed to assess age-related extracellular matrix (ECM) protein levels in the MCC. The histological sections were also used for Alcian blue histochemistry to detect glycosaminoglycans (GAGs). Results: GO enrichment analysis revealed that the genes related to “extracellular matrix organization,” including Acan, Col1a1, Col1a2, Col2a1, Mmp3, Mmp9, and Mmp13, were most differentially expressed in the aged mandibular condyle. Among these seven genes, Mmp3 was upregulated, and the others were downregulated with aging. Histological examination showed the age-related morphological and histological changes in the MCC. Immunohistochemical investigation showed the localization of matrix metalloproteinases (MMPs)-3, -9, and -13 and their substrate proteins, aggrecan, type I collagen, and type II collagen, in the mandibular condyle at 10 and 50 weeks, indicating different localizations between the young and the aged. In the aged MCC, semi-quantitative immunohistochemistry showed a significant decrease in the aggrecan protein level, and Alcian blue histochemistry showed a decrease in GAGs. Conclusion: MMP-3, MMP-9, and MMP-13 contribute to the remodeling of the ECM of the MCC and subchondral bone during aging by degrading ECM proteins at specific times and sites under the regulation of their production and secretion.

Tuina Intervention in Rabbit Model of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is mainly characterized by degenerative changes in the knee joint's cartilage and surrounding soft tissues. The efficacy of Tuina in treating KOA has been confirmed, but the underlying mechanism needs to be investigated. This study aims to establish a scientifically feasible KOA rabbit model treated with Tuina to reveal the underlying mechanisms. For this, 18, 6-month-old normal-grade male New Zealand rabbits were randomly divided into sham, model, and Tuina groups, with 6 rabbits in each group. The KOA model was established by injecting 4% papain solution into the knee joint cavity. The Tuina group was intervened with Tuina combined with the knee joint rotary correction method for 4 weeks. Only the standard grasping and fixation were performed in sham and model groups. At the end of the 1-week intervention, the knee joint range of motion (ROM) was observed, and cartilage hematoxylin-eosin (HE) staining was done. The study shows that Tuina could inhibit chondrocyte apoptosis, repair cartilage tissue, and restore knee joint ROM. In conclusion, this study demonstrates the scientific feasibility of Tuina treatment for KOA model rabbits, highlighting its potential application in the study of KOA and similar knee joint-related conditions.

Added Value of MRI Knee Cartigram in Assessment of Anterior Knee Pain in Comparison to Conventional Standard MRI

Background Osteoarthritis (OA) is a multi-tissue, multi-factorial disease and worldwide a major cause of disability resulting from reduced joint mobility and function. Progressive loss of hyaline cartilage is one of the hallmark features of osteoarthritis, initiated by a loss of proteoglycans and an increase in water content, followed by a loss of type II collagen and a change in collagen fiber orientation. Objective To evaluate the role of T2 mapping in detection of degenerative changes in articular cartilage of knee joint as compared to standard clinical magnetic resonance imaging (MRI) at 1.5T. Patients and Methods From April 2020 to November 2020, this prospective Study was done to use T2 mapping to visualize the articular cartilage of the knee on 1.5 T MR Scanner using special software to evaluate the efficiency Of T2 mapping to detect cartilage lesions. The material of this study included 380 patients. The study includes all of them come complaining of knee pain and 2 of them had previous minor knee trauma, each patient had a single MRI exanimation including conventional MRI routine protocol and added a single complementary T2 mapping. Results there were significant differences between T2 mapping and conventional MRI sequence in the ability to detect cartilage degeneration as T2 mapping was capable of detecting all lesions that were visible on the clinical MRI. Moreover, T2 mapping showed more cartilage lesions than clinical MRI T2 mapping showed more cartilage lesions than clinical MRI, and in T2 maps the lesions appeared generally wider. This proposes that T2 mapping is feasible in the clinical setting and may reveal cartilage lesions not seen on the standard knee MRI. Conclusion Our results suggest that T2 mapping is an interesting MRI sequence for the exploration of patients articular cartilage in and should be included in the routine protocol if cartilage pathology is suspecting as it may improve the diagnostic accuracy of MRI for focal chondral lesions, and should help decide whether and MR-arthrography or CT-arthrography is necessary.

Shear wave elastography and T2* mapping in the detection of early-stage trochlear cartilage damage.

The presence of degenerative changes in joint cartilage is one of the major features in osteoarthritis. To investigate the contribution of shear wave elastography and T2* mapping to the early diagnosis of femoral trochlear cartilage damage. A total of 30 individuals whose trochlear cartilage structure was evaluated as normal in conventional magnetic resonance imaging (MRI) sequences (control group) were prospectively compared with 30 patients who had early-stage cartilage damage findings on conventional MRI (study group), by performing B-mode ultrasonography, shear wave elastography, and T2* mapping. Cartilage thickness, shear wave, and T2* mapping measurements were recorded. After evaluating B-mode ultrasound and conventional MRI sequences, cartilage thickness was found to be significantly higher in the study group on both B-mode ultrasound and MRI. Shear wave velocity values of the study group (medial condyle [MC] 4.65 ± 1.11 m/sn, intercondylar [IC] 4.74 ± 1.20 m/sn, and lateral condyle [LC] 5.42 ± 1.48 m/sn) were observed to be significantly lower than the control group (MC 5.60 ± 0.77 m/sn, IC 5.85 ± 0.96 m/sn, and LC 5.63 ± 1.05 m/sn) (P < 0.05). T2* mapping values were significantly higher in the study group (MC 32.38 ± 4.04 ms, IC 35.78 ± 4.85 ms, and LC 34.04 ± 3.40 ms) than that of the control group (MC 28.07 ± 3.29 ms, IC 30.63 ± 3.45 ms, and LC 29.02 ± 3.24 ms). Shear wave elastography and T2* mapping are reliable methods for evaluating early-stage trochlear cartilage damage.

Degenerative changes through MR cartilage mapping in anterior cruciate ligament-reconstructed knees

BackgroundAnterior cruciate ligament (ACL) injury increases risk for post traumatic knee osteoarthritis. ACL injury causes lack of knee stability and frequently requires ACL-reconstruction (ACLR) in order to restore functional and anatomical joint stability. Magnetic resonance imaging with T2 mapping sequence is used to quantify the amount of water content in articular cartilage hence; it is considered a better tool and more beneficial than radiographic based assessment in early detection even before being symptomatic. The aim of work is to estimate the incidence of subclinical degenerative changes that happened early in patients who underwent ACL reconstruction and to identify the correlations of T2 mapping values with patients' BMI, meniscal state/operations, ACL graft assessment and presence of ACLR related complications.ResultsThe study was conducted upon 71 patients, divided into 61 anterior cruciate ligament reconstructed knees and 10 control cases using 1.5 T MRI. Assessment of cartilage sub-compartment T2 values and comparison with average normal cartilage T2 values obtained from the control group. Multiple correlations of the grade of articular cartilage degeneration within anterior cruciate ligament reconstructed knees with Body Mass Index (BMI), time of operation as well associated meniscal operations and anterior cruciate ligament graft complications.ConclusionsAdding the T2 cartilage mapping sequence improves the ability to detect subclinical early degenerative articular cartilage changes in patients who underwent anterior cruciate ligament reconstruction, taking into consideration the relation of the patients' BMI, previous meniscal injuries/operation, ACL graft status and related graft complications with the T2 cartilage mapping values.

Bevacizumab suppressed degenerative changes in articular cartilage explants from patients with osteoarthritis of the knee

BackgroundThis study was designed to test the hypothesis that blockade of vascular endothelial growth factor (VEGF) suppresses degenerative changes in articular cartilage from patients with osteoarthritis (OA).MethodsArticular cartilage from eight OA patients was subjected to explant culture for 2 days in the presence or absence of 10 ng/ml recombinant interleukin (IL)-1β. The blocking effect of VEGF was examined by the addition of 10 or 100 ng/ml of bevacizumab. The culture media were harvested, and markers for cartilage degradation were measured by sandwich enzyme-linked immunoassay. Total RNA was isolated from cartilage tissues, and gene expressions associated with the anabolic response were examined by the quantitative real-time polymerase chain reaction.ResultsBevacizumab significantly reduced concentrations of matrix metalloproteinase (MMP)-2, MMP-3, and cartilage oligomeric matrix protein in the culture media with and without IL-1β. Significant suppressive effects of bevacizumab on MMP-9 and MMP-13 were shown only in the presence of IL-1β. Gene expression of Col2a1 was significantly increased by the addition of bevacizumab in the absence of IL-1β.ConclusionBevacizumab inhibits catabolic reactions and stimulates anabolic function in articular cartilage derived from OA patients directly, suggesting a protective effect on articular cartilage from OA progression.

The Localizations of Osteoarthritis in the Knee, Ankle and Foot Joints of Cadaver: Comparison in Radiological, Morphological and Histopathological Aspects

Objective: Osteoarthritis (OA) is the most common joint disease. In this study it was aimed to compare the general features of OA such as location, placement, severity and shape of the lesions in terms of radiological and morphological aspects and to determine their relationship with each other. Methods: In our study, the antero-posterior and lateral radiographies of knee talocrural and transverse tarsal joints of 20 cadavers by age between 30 and 50 years were taken. The results obtained from the radiological examination were graded according to the Kellgren and Lawrence scale. For each of the identified regions, the presence of degenerative changes was noted. Then samples were taken from these regions were examined by microscopic methods. The cartilage degeneration changes, presence of fibrillations, density, depth, chondrocyte aggregation, and necrotic changes were evaluated. Results: In the radiological examination OA was found in 35% in knee joint, 25% in the talocrural joint, 15% in the transverse tarsal joint. In the morphological examination OA was found in 31.5% knee joint, 25% ankle joint and 5% transverse tarsal joint. In the microscopic examination OA was found in 94.7% knee joint, in 94.7% ankle joint and in 100% transverse tarsal joint. Conclusion: Although radiological and macroscopic OA was detected in approximately 1/3 of cadavers aged between 30 and 50 years, degeneration of varying degrees was detected in all joints examined in microscopic examination. This shows that an advanced age disease OA, starts at a very early age.

Results of Arthroscopic Treatment for Femoroacetabular Impingement

Background. Femoroacetabular impingement (FAI) is one of the most frequent causes of hip pain and limited hip mobility in young and middle-aged patients. It is a result of repeated injury of hip structures, that leads to degenerative changes in hip labrum, cartilage and subchondral bone and provokes progressive development of hip osteoarthritis.&#x0D; Aim of study to analyze own experience of treating patients with femoroacetabular impingement and identify factors affecting its outcomes.&#x0D; Methods. Retrospective, uncontrolled, single-center clinical study included 128 patients with FAI which had 150 surgeries on 149 joints in in the period from 2013 to 2021. All patients underwent physical examination and X-ray diagnostics, their FAI type was identified. The alpha angle of external part of femoral head in anterior-posterior position and in the modified Dunn 45 position, as well as Tonnis angle, lateral central-marginal angle in Ogata modification and the height of articular gap along the lateral (LS) and medial edges (MS) of sclerosed acetabulum part were calculated. The i-HOT-33 and HOS scales were used to assess preoperative status and postoperative results.&#x0D; Results. The average follow-up period was 3.9 years (SD 1.71; min 1.05 and max 8.16). The study included 55 (43.0%) women and 73 (57.0%) men which underwent 64 (42.7%) and 86 (57.3%) surgeries respectively. The most common types of FAI, according to our data, were mixed type (53% of joints) and сam type (27.5% of joints). Insufficient coverage of the femoral head by the acetabulum (borderline dysplasia) in combination with the сam deformity of the femoral head was observed in 18.1%. Pincer-type FAI was observed in 1.4% of joints. We obtained the worst results with a combination of сam deformity and borderline dysplasia in comparison with cam- and mix-type FAI according to the i-HOT-33 and HOS scales. Patients age, deep cartilage damage, irreparable labrum damage and height decrease of the lateral part of the articular gap determined negative effect on treatment results according to the i-HOT-33 and HOS scales.&#x0D; Conclusion. Hip arthroscopy showed good short- and midterm outcomes in patients with FAI. Pain syndrome is most often manifested in patients with pathology of hip soft tissue structures concomitant to FAI. The combination of сam deformity and insufficient femoral head coverage, deep cartilage damage and a height decrease of the articular gap are important predictors of poor treatment results.

Mapping knowledge landscapes and emerging trends of the links between osteoarthritis and osteoporosis: A bibliometric analysis.

Osteoarthritis has the characteristics of degenerative changes in articular cartilage and secondary osteoporosis, and it is a common chronic irreversible joint disease. In addition to affecting articular cartilage, subchondral bone, joint capsule and synovial membrane also undergo pathological changes during the development of the disease. Multiple studies have revealed that patients with osteoarthritis were found to have a significantly increased risk of osteoporosis, which also contributes to the progression of osteoarthritis. However, in the current existing studies, we found that no scholars have used bibliometric analysis in the study of the relationship between osteoarthritis and osteoporosis. From the perspective of bibliometrics, this study summarizes in detail the degree of cooperation between countries, research institutions, authors, and related journals in the field of osteoarthritis and osteoporosis research and their respective influence. In this way, the evolution of knowledge structure, the change of research focus and the hot topics with research potential in the future can be further visualized and analyzed. Search the Web of Science core collection in Science Citation Index Expanded for articles and reviews of research on osteoarthritis and osteoporosis from 1998 to 2021. Bibliometric tools such as VOSviewer, CiteSpace, were be frequently used in our study. They are mainly used to analyze collaborations between countries, research institutions, and publication authors. Meantime, co-citation analysis of journals, co-occurrence analysis of keywords and subject categories will also be reflected in the study. According to the search strategy, 1,078 publications were included during the period 1998-2021. And the number of annual publications on the relationship between osteoarthritis and osteoporosis is on the rise. The United States has achieved the most and contributed the most in this field and the Boston University was the most prolific institution. For the statistical analysis of published publications, Reginster JY had the highest number of publications, while Felson DT had the highest co-citation frequency. Respectively, Osteoarthritis And Cartilage was the most productive journal in this area of research. The keywords "inflammation," "expression," and "mesenchymal stem cells" may also be the development trend and research hotspot of the future research direction in this field. In our study, the relationship between osteoarthritis and osteoporosis was analyzed by using literature measurement. These analysis results can lead researchers to learn more directly about the trend in this area and provide guidance for determining popular research directions.

Knee Diameter and Cross-Section Area Measurements in MRI as New Promising Methods of Chondromalacia Diagnosis-Pilot Study.

Background and Objectives: Chondromalacia often affects the knee joint. Risk factors for the development of cartilage degenerative changes include overweight, female sex and age. The use of radiological parameters to assess the knee joint is rarely reported in the literature. Materials and Methods: The study involved 324 patients, including 159 (49%) women and 165 (51%) men, with an age range between 8–87 years (mean: 45.1 ± 20.9). The studied group had a body mass index (BMI) in the range of 14.3–47.3 (mean: 27.7 ± 5.02). A 1.5 Tesla and 3.0 Tesla (T) MRI scanner was used to assess the cartilage of the knee joint using the Outerbridge scale. The radiological parameters analyzed were the Insall–Salvati index, knee surface area, knee AP (antero-posterior) maximal diameter and knee SD (sinistro-dexter) maximal diameter. Results: Parameters such as the knee surface area, knee AP maximal diameter and knee SD maximal diameter showed a significant correlation with Outerbridge Scale (p < 0.014). The age of the patients showed a significant correlation with each knee parameter (p < 0.004). Results of knee AP and SD maximal diameter measurements strongly depended on BMI level. Conclusions: A significant relationship was found between the knee surface area, knee AP maximal diameter and knee SD maximal diameter and the advancement of chondromalacic changes in the knee joint, age and BMI.

Local Drug-Induced Modulation of gp130 Receptor Signaling Delays Disease Progression in a Pig Model of Temporo-Mandibular Joint Osteoarthritis

Temporomandibular joint disorders (TMJs) are a multifaceted group of chronic disorders characterized by stiffness in the jaw, limited jaw mobility and pain when opening or closing the mouth. TMJs are relatively common, with incidence rates in the range of 5–12%, with nearly twice as many women as men being affected. One of the primary causes of TMJs is a degenerative disease of joints, such as osteoarthritis (OA), characterized by progressive loss of cartilage which causes stiffness, swelling, and pain. Currently, there are no disease-modifying agents on the market for OA. We have recently discovered a small molecule, R805 acting as a modulator of glycoprotein 130 (gp130) receptor for IL-6 family of cytokines. R805 enables regenerative outputs of endogenous joint stem and progenitor cells through immunomodulation in the joint microenvironment by reducing the levels of destructive cytokines and supporting chondrocyte survival and anabolism. Extensive testing has shown R805 to be safe at doses far above the therapeutic level. Here, we have conducted a pivotal efficacy study in our newly-established pig model of TMJ post-traumatic OA. IA injection of R805 has shown a highly significant reduction of articular cartilage degeneration, reduced synovitis and degenerative changes in subchondral bone in the mandibular condyle compared to the vehicle-treated group. These data will support additional pre-clinical development of R805 as a first-in-class injectable therapeutic for TMJ osteoarthritis.