Advanced-stage Osteoarthritis Research Articles

Intra-articular autologous conditioned plasma reduces pain in early osteoarthritis and improves stiffness in advanced osteoarthritis knee: a prospective observation

Background: In this study, we aimed to investigate the effects of single-dose intra-articular autologous conditioned plasma injection as the treatment for early and advanced osteoarthritis knee. Methods: A single centre-based prospective observational analysis was conducted among patients who opt for conservative management by intra-articular autologous conditioned plasma Injection between July 2022 to June 2023. Total 46 patients were included and analysed in study on 1, 3, and 6 months’ follow-up after ACP injection. The WOMAC score and its sub scores were analysed and compared pre-procedure and on subsequent follow ups. Results: A total of 46 patients were analysed in the study, with male predominance of 56.5% with mean BMI of 27.37±5.35. On KL grading, 34.8% patients had KL grade II Osteoarthritis, 52.2% had grade III and 13.0% had grade IV. On comparison of WOMAC score and its sub-scales, all the values were found to be statically significant while comparing before injection (p value <0.0001) and one month follow up and before injection and six months’ follow-up (p value <0.0001). Conclusions: Six months following intra-articular autologous conditioned plasma injection, there was a noteworthy decrease in pain in early stages of osteoarthritis and improvement in knee stiffness in advanced stages of osteoarthritis as compared to the pre-treatment state.

Advanced MR Imaging for Knee Osteoarthritis: A Review on Local and Brain Effects

Knee osteoarthritis is one of the leading causes of chronic disability worldwide and is a significant social and economic burden on healthcare systems; hence it has become essential to develop methods to identify patients at risk for developing knee osteoarthritis at an early stage. Standard morphological MRI sequences are focused mostly on alterations seen in advanced stages of osteoarthritis. However, they possess low sensitivity for early, subtle, and potentially reversible changes of the degenerative process. In this review, we have summarized the state of the art with regard to innovative quantitative MRI techniques that exploit objective and quantifiable biomarkers to identify subtle alterations that occur in early stages of osteoarthritis in knee cartilage before any morphological alteration occurs and to capture potential effects on the brain. These novel MRI imaging tools are believed to have great potential for improving the current standard of care, but further research is needed to address limitations before these compositional techniques can be robustly applied in research and clinical settings.

Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis.

This study aimed to analyze the relationship between vascular endothelial growth factor A (VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. The most common nucleotides in both knee OA subjects and healthy controls were CC for -2578C/A, GG for -1154G/A, CG for -634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA -2578C/A, -1154G/A, -634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of -634C/C genotype were significantly higher in OA patients than in the controls (P = 0.035). According to the -2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA (P = 0.023). VEGFA -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the -2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.

Stage-specific and location-specific cartilage calcification in osteoarthritis development

ObjectivesThis study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies.MethodsNormal and OA cartilages were serially sectioned for micro-CT, scanning...

Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation.

Osteoarthritis (OA) is an age-related degenerative disease, and its incidence is increasing with the ageing of the population. Metformin, as the first-line medication for the treatment of diabetes, has received increasing attention for its role in OA. The purpose of the present study was to confirm the therapeutic effect of metformin in a mouse model of OA and to determine the mechanism underlying the resultant delay in OA progression. The right knees of 8-week-old C57BL/6 male mice were subjected to destabilization of the medial meniscus (DMM). Metformin (200 mg/kg) was then administered daily for 4 or 8 weeks. Safranin O-fast green staining, H&E staining and micro-CT were used to analyse the structure and morphological changes. Immunohistochemical staining was used to detect type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), NOD-like receptor protein 3 (NLRP3), caspase-1, gasdermin D (GSDMD) and IL-1β protein expression. Reverse transcription-quantitative PCR was used to detect the mRNA expression of NLRP3, caspase-1, GSDMD and IL-1β. Histomorphological staining showed that metformin delayed the progression of OA in the DMM model. With respect to cartilage, metformin decreased the Osteoarthritis Research Society International score, increased the thickness of hyaline cartilage and decreased the thickness of calcified cartilage. Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1β. In addition, in subchondral bone, metformin inhibited osteophyte formation, increased the bone volume fraction (%) and the bone mineral density (g/cm3), decreased the trabecular separation (mm) in early stage of osteoarthritis (4 weeks) but the opposite in an advanced stage of osteoarthritis (8 weeks). Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis.

Functional Outcome of Rotating Platform Versus Fixed Platform of Total Knee Arthroplasty- A Comparative Study

Background: Total knee arthroplasty (TKA) has shown to be a successful and reliable procedure for older, debilitatedpatients with knee osteoarthritis. TKA’s indications were widened to include younger and more active patients after itsinitial success.Objectives: To compare the functional outcome of rotating vs fixed platform of total knee arthroplastyMethods: All patients who are fit to undergo total knee arthroplasty like advanced stages of osteoarthritis and rheumatoidarthritis in age group of 50-70 years . We compared the functional outcome between rotating platform versus fixedplatform of Total Knee Arthroplasty. Clinical and radiological follow-up was performed at 1, 3, 6 months and 1year afterthe operation. Pre-operative and follow-up ratings according to Knee Society Scoring system were obtained for all thepatients. In addition, a visual analogue scale was used to specially assess the severity of the painResults: In group A and group B there were 6 males (30%) and 14 females (70 %). In both the groups the mean postoperative range of movements were significantly improved for the follow-up at every 3months with the mean ROM of120° achieved at 1year follow-up. The ROM has significantly improved from 90° at 3rd month follow- up to 120° at 1yearfollow-up. The mean KSS knee and functional score were gradually improved in post operatively in 3rd, 6th and 1yearfollow-up compared to the pre operative KSS score.Conclusion: The post-operative range of motion and the Knee Society functional score were similar in both groups. Therewas no significant statistical difference between the two groups of Total Knee Arthroplasty in terms of post-operativerange of motion and functional outcomes.

FUNCTIONAL OUTCOME IN EARLY OSTEOARTHRITIS OF KNEE WITH TWO DOSES OF PLATELET RICH PLASMA OUR EXPERIENCE.

Background: Osteoarthritis (OA) is a degenerative disorder of synovial joints in which there is gradual softening and disintegration of articular cartilage accompanied by the new growth of cartilage and bone at the joint margins(Osteophytes), cyst formation and sclerosis in the subchondral bone, mild synovitis, and capsular brosis. It differs from simple wear and tears in that it is asymmetrically distributed, often localized to only one part of a joint i.e., weight bearing, and often associated with abnormal loading rather than frictional wear. It is a dynamic phenomenon and shows features of both destruction and repair. Cartilage softening and disintegration are accompanied from the very outset by hyperactive new bone formation, osteophyte formation and remodeling. Osteoarthritis is an age-related phenomenon, and it affects more than 80% of people greater than 55 years of age. Body mass index (BMI) plays a vital role in osteoarthritis in weight-bearing joints. People with obese or overweight were approximately 4.6 times more likely to have knee OA than normalweight individuals. In addition people with metabolic and endocrine disorders are also more prone for osteoarthritis at an early age. Methods: Sixty patients suffering from grade1and 2 osteoarthritis knee joint who attended the outpatient department of orthopaedics, King George hospital, Visakhapatnam between November 2018 to October 2020 were included in the study. Informed and written consent was taken from the patients. General physical examination was done. Neurovascular status of both lower limbs was also examined. X-ray of both knee joints in antero-posterior and lateral views were taken in standing position. Routine pre-injection WOMAC and VAS score were recorded. Under aseptic conditions, two platelet-rich plasma (PRP) injections were injected into the knee joint at four weeks interval. Functional status of the knee was evaluated using WOMAC and VAS score at one, three and six week's interval. This study is a anlyticl comparative study. Results: There is a signicant difference in the VAS score and WOMAC score before giving an injection and after giving an injection, in patients with grade 1 and grade 2 osteoarthritis. The visual analogue score showed a mean of 7.16 at pre-injection period, which decreased to 5.95 at 1st week and 4.81 at 3rd week and 4.06 at six weeks follow up. Conclusion: In the present study the effectiveness of two aliquots of PRP injection was evaluated. Although studies including more than 2 PRP injections and more advanced stages of osteoarthritis were compared, the time frame was xed to 6 weeks. The functional outcome of the patient was better after 2nd dose of PRP. The present study concluded that two doses of PRP injection decreases the joint pain, alleviates the symptoms and enhances the activity of daily living and quality of life in short term duration.

A Kinesio Taping Method Applied in the Treatment of Postsurgical Knee Swelling after Primary Total Knee Arthroplasty.

Background The knee is one of the joints in the human body that is most susceptible of osteoarthritis (OA). In the case of advanced-stage OA, total knee arthroplasty (TKA) is a treatment of choice. One modern physiotherapeutic method to support the treatment in the early postsurgical period is Kinesio Taping (KT). The aim of this study is to evaluate the efficacy of KT on swollen subcutaneous tissue after TKA. Materials and methods. The studied group consisted of 23 patients who had received TKA. The mean BMI was 30.60 ± 4.91, and KT was applied between the 3rd and 8th day of the early postoperative period. The control group was constituted by 22 patients who had received TKA. The mean BMI was 30.41 ± 6.00, and KT was not applied. On the 3rd and 8th day after TKA, in all patients, the swelling of the shin, range of motions (ROM), and pain were measured using ultrasound, a goniometer, and a VAS scale, respectively. Results. In the KT group, the lateral measurement at the top of the head of the fibula significantly decreased between the 3rd and 8th day (11.47 ± 0.76 vs. 9.76 ± 0.77; p = 0.0004). The knee flexion angle on day 3 was statistically significantly different from that on day 8 (48.61 ± 3.08 vs. 72.74 ± 3.92; p = 0.00004). The evaluation results for severity of pain using the VAS scale on day 3 were statistically significantly higher than those on day 8 (5.74 ± 0.25 vs. 4.30 ± 0.25; p = 0.00006). In the group of patients to whom KT was not applied, the lateral measurement at the top of the head of the fibula on day 3 was not statistically significantly different from that on day 8 (10.323 ± 0.828 vs. 10.273 ± 0.995; p = 0.9227). The knee flexion angle in the group that did not receive KT on day 3 was statistically significantly different from that on day 8 (45.182 ± 3.654 vs. 59.909 ± 4.817; p = 0.0006). The severity of pain evaluated using the VAS scale on day 3 was statistically significantly different from that on day 8 (6.227 ± 0.146 vs. 4.864 ± 0.190; p = 0.0001). Conclusions. KT is an effective method for improving subcutaneous drainage and decreasing subcutaneous tissue. However, KT does not affect postoperative pain and ROM.

PMS17 Patient and Provider Factors Associated with Aseptic Loosening Following Cemented Primary Knee Total Arthroplasty

Total Knee Replacement (TKR) is a commonly used intervention in the treatment of advanced stage osteoarthritis. Aseptic loosening, a failure of the prothesis-bone fixation in the absence of infection, is the most common cause of revision. Several studies have investigated risk factors associated with aseptic loosening, though identification of patients at risk remains elusive. There is a need for foundational work which further investigates factors associated with aseptic loosening.

Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model.

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis.

The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

Canine developmental elbow disease part 1: aetiopathogenesis and diagnosis

Elbow dysplasia or ‘developmental elbow disease’ as it is now known, is an umbrella term encompassing multiple abnormalities of the elbow joint. These include elbow incongruity, fragmented medial coronoid process, osteochondritis dissecans and ununited anconeal process. These problems may occur individually or in combination with each other and all may cause lameness, pain, reluctance to exercise and restricted movement as the disease progresses. The advanced stage of osteoarthritis associated with medial coronoid disease involving extensive damage to or loss of cartilage is known as medial compartment disease. There are multiple modalities available for imaging the elbow joint: radiography which is widely available in general practice can detect some changes but may miss others; computed tomography in conjunction with arthroscopic examination is considered the ‘gold standard’ in elbow imaging. Part 1 of this two part series of articles introduces the aetiopathogenesis of canine developmental elbow disease, and part 2 will cover the surgical and nonsurgical management.

Single use instruments for total knee arthroplasty.

Aim Total knee arthroplasty represents a procedure that is successfully performed to relieve functional limitation and pain in advanced stages of osteoarthritis. In the next 20 years the number of these procedures will be increased about four times. Patient specific instrumentation (PSI) has been introduced in the past years. The aim of this study was to evaluate whether SUI are more useful in clinical, organizational and economic terms. Methods A database search about single use instrumentation (SUI) was conducted on PubMed and Google Scholar for the period 2010-2020 using the following key "total knee replacement", "total knee arthroplasty", "single use instruments", and "disposable instruments". The results of the selected studies were classified according to clinical, economic and organizational criteria. Results The main advantage of SUI has been reported to reduce costs, timely turnover of operating rooms, maximizing the operating room utilization and patient throughput, improving the number of outpatient total joint replacements. No difference has been found other than with regard to conventional instruments in terms of clinical outcome such as hip-knee-ankle angle and other radiographic parameters, Oxford Knee Score, while a decreased infection rate has been demonstrated. Regarding the economic aspect, a reduction of direct and indirect reduction of costs has been shown for the cost of instruments reprocessing, tray sterilization, 90-day infection rate. Conclusion The SUI can be an alternative to conventional instruments, but there are still few studies in the literature regarding clinical outcomes.

Intra-Articular Methylprednisolone Injection for Advanced Osteoarthritis in Geriatric Patient Population

Background: We aimed to investigate the effect of intra-articular methylprednisolone injection on pain and functional outcomes and the number of outpatient clinic admissions in patients with advanced knee osteoarthritis in the geriatric age group. Method: The files of 78 patients over the age of 65 who were administered intra-articular methylprednisolone injection with the diagnosis of primary gonarthrosis between 2018 and 2020 were analyzed retrospectively. Age, gender, and affected side of the patients were recorded. The number of outpatient clinic admissions, VAS and Womac scores before and after injection were evaluated statistically. Results: Of the patients, 18 were male (24.7%) and 55 were female (75.3%). The mean age was 74.95±7.11 years. The values of the patients' WOMAC and VPS scores at the 1st and 3rd months were significantly lower than the pre-injection period. Compared to the number of outpatient visits in the 6-month period before injection, the decrease in the number of outpatient visits in the 6-month period after injection was statistically significant. A strong positive correlation was found between the number of outpatient visits before injection and the first VPS score. Conclusions: In geriatric patients with advanced-stage osteoarthritis who do not accept total knee arthroplasty, intra-articular methylprednisolone injection may be a feasible method that reduces pain and the number of outpatient visits in the short term.

Clusterin Is Associated with Systemic and Synovial Inflammation in Knee Osteoarthritis.

This study aimed to determine possible associations between transcriptional and translational levels of clusterin (CLU) in the systemic and local joint environments with the severity of knee osteoarthritis (OA) and to investigate CLU mRNA expression in knee OA fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor-α. Circulating and synovial fluid CLU levels in 259 knee OA patients were quantified using an enzyme-linked immunosorbent assay. Relative CLU mRNA expression in 50 knee OA synovial tissues and 4 knee OA FLSs was determined using real-time polymerase chain reaction. Plasma CLU levels of knee OA patients were significantly higher than paired synovial fluid samples. Compared with early-stage knee OA patients, those with advanced-stage OA had considerably increased plasma and synovial fluid CLU levels. There were significant positive associations of plasma and synovial fluid CLU levels with radiographic severity of knee OA. Plasma CLU levels were directly correlated with its synovial fluid levels and high-sensitivity C-reactive protein levels in the patients. Receiver-operating characteristic curve analysis unveiled the potential utility of plasma CLU as a novel biomarker for knee OA severity (AUC = 0.80), with a sensitivity of 71.4% and a specificity of 73.3%. Marked upregulation of CLU mRNA expression was observed in both the inflamed synovial tissues and FLSs of knee OA. Increased CLU mRNA and protein levels in the systemic and local joint environments of knee OA might reflect knee OA severity, especially systemic and synovial inflammation.

Meniscal Root Tears and Extrusion Are Significantly Associated with the Development of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

To identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development. From the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models. A total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24). We identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.

Incidence of Mucoid Degeneration of Cruciate Ligaments in Patients Undergoing Primary Total Knee Replacements – A Study of 42 Knees

Mucoid degeneration of the ACL is largely an underdiagnosed condition. These are often misjudged as partial tears of ACL on routine MRI evaluation. Here we histologically analyse the incidence of mucoid degeneration of the cruciate ligaments in 32 patients who underwent primary total knee arthroplasty in our institute. 10 among them had bilateral total knee replacements making the total sample size 42 knees. ACL samples were sent for histopathological evaluation from 41 knees (one knee was an ACL deficient knee), and PCL samples were sent from patients who underwent total knee replacements with posterior stabilising implants. out of these 41 samples of ACL, 60.9 % turned out to be positive for mucoid degeneration. 9 out of 13 PCL samples (69.5%) turned out to be having mucoid degeneration. This study shows that the real incidence of mucoid degeneration of cruciate ligaments is much more than what is reported in literature. This emphasises the role of preoperative MRI to look for coexisting painful mucoid degeneration even in elderly patients with early osteoarthritis, which is an arthroscopically treatable condition thus delaying the total knee replacements in these patients. The higher incidence of mucoid degeneration in cruciate ligaments associated with advanced arthritis raises the question of functional integrity of PCL in these patients, making the use of posterior stabilising implants more advisable in patients with advanced stages of osteoarthritis.

Differential Expression Patterns of Rspondin Family and Leucine-Rich Repeat-Containing G-Protein Coupled Receptors in Chondrocytes and Osteoblasts.

Objective Rspondins (RSPOs) are regarded as the significant modulators of WNT signaling pathway and they are expressed dynamically during developmental stages. Since in osteoarthritis (OA) both cartilage and subchondral bone suffer damages and WNT signaling pathway has a crucial role in their maintenance, the objective of the study was to analyze expression profile of RSPO family and its receptors [leucine-rich repeat-containing G-protein coupled receptors (LGRs)] in OA tissue samples as well as in differentiating chondrocytes and osteoblasts. Materials and Methods:In this experimental study, human early and advanced stage of OA tissue samples were analyzed for the morphological changes of articular cartilage by hematoxylin and eosin (H&E) staining, safranin-O staining and lubricin immunostaining. RSPOs and LGRs expression were confirmed by immunohistochemistry. Human primary chondrocytes and human osteoblast cell line, SaOS-2, were cultured in differentiation medium till day 14 and they were analyzed in terms of expression of RSPOs, LGRs and specific marker for chondrogenesis and osteogenesis by western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). ResultsAdvanced stage OA tissue samples showed increased expression of RSPO1 and LGR6 in a region close to subchondral bone. While RSPO2 and LGR5 expression were seen overlapping in the deep region of articular cartilage. Differentiating chondrocytes demonstrated elevated expression of RSPO2 and LGR5 from day 7 to day 14, whereas, osteoblasts undergoing differentiation showed enhanced expression of RSPO1 and LGR6 from day 2 to day 14. Under tumor necrosis factor alpha (TNFα) stimulatory conditions, RSPO2 and RSPO1 recovered the suppressed expression of inflammatory, chondrogenic and osteogenic markers, respectively. A recovery in the stability of β-catenin was also noticed in both cases. Conclusion:Spatial expression of RSPOs during progression of OA might be dynamically controlled by cartilage and subchondral bone. Interplay amid chondrocytes and osteoblasts, via RSPOs, might provide probable mechanisms for treating inflammatory pathogenic conditions like OA.

Deep Learning Predicts Total Knee Replacement from Magnetic Resonance Images

Knee Osteoarthritis (OA) is a common musculoskeletal disorder in the United States. When diagnosed at early stages, lifestyle interventions such as exercise and weight loss can slow OA progression, but at later stages, only an invasive option is available: total knee replacement (TKR). Though a generally successful procedure, only 2/3 of patients who undergo the procedure report their knees feeling “normal” post-operation, and complications can arise that require revision. This necessitates a model to identify a population at higher risk of TKR, particularly at less advanced stages of OA, such that appropriate treatments can be implemented that slow OA progression and delay TKR. Here, we present a deep learning pipeline that leverages MRI images and clinical and demographic information to predict TKR with AUC 0.834 ± 0.036 (p < 0.05). Most notably, the pipeline predicts TKR with AUC 0.943 ± 0.057 (p < 0.05) for patients without OA. Furthermore, we develop occlusion maps for case-control pairs in test data and compare regions used by the model in both, thereby identifying TKR imaging biomarkers. As such, this work takes strides towards a pipeline with clinical utility, and the biomarkers identified further our understanding of OA progression and eventual TKR onset.

The interactions between MRI-detected osteophytes and bone marrow lesions or effusion-synovitis on knee symptoms in patients with knee osteoarthritis

Purpose: Early diagnosis of osteoarthritis (OA) facilitates early treatment to prevent disease progression. Osteophytes (OPs) have long been regarded as landmark structural changes of OA. However, radiography can only detect OPs in the advanced stage of OA. Magnetic resonance imaging (MRI) has higher sensitivity than radiography, and can detect OPs at an earlier stage of OA. Previous studies were controversial about the relationship between OPs and knee symptoms, and few researches focused on the interactions between OPs and other structure changes on the progression of knee symptoms.