Articular Cartilage Thickness Research Articles

Efficacy and safety of magnet therapy using portable device for knee osteoarthritis. 55-week double-blind study results

To study the efficacy and safety of long-term use of the portable magnet therapy device ALMAG+ (Almag Active) in knee OA (KOA). A double-blind, randomized, placebo-controlled, prospective, 55-week clinical trial of the medical device was conducted. The study included patients with primary and secondary (associated with immunoinflammatory rheumatic diseases) KOA stages I-III according to Kellgren-Lawrence diagnosed using generally accepted criteria (R. Altman et al., 1986). Enrollment of patients with secondary KOA was allowed given that the remission or low disease activity was achieved. During the study patients had to receive steady drug therapy. No intra-articular injections of glucocorticosteroids, hyaluronic acid, PRP, and physiotherapy procedures for knees (electrotherapy, shockwave therapy, heat therapy, hydrotherapy, peloid therapy) were allowed three months or less before the enrollment and throughout the study. According to the approved protocol, 77 patients (mean age 52.73±12.97 years) from two research centers participated in the study: 32 (41.6%) were males, and 45 (58.4%) were females. Primary KOA occurred in 41 (52%) patients, 36 (46.8%) patients had secondary KOA (associated with rheumatoid arthritis, ankylosing spondylitis, Sjögren's disease, psoriatic arthritis, systemic lupus erythematosus, or diffuse scleroderma). All patients received NSAIDs as a concomitant therapy, 24.7% received diacerein, 28.6% received disease-modifying anti-rheumatic drugs, 2.6% received methylprednisolone up to 8 mg/day, and 9% received biologic therapy. After randomization, 40 (52%) patients received placebo treatments (Group 1) and 37 (48%) received active treatments (Group 2). Both groups were comparable in the main parameters. The proportion of smokers was higher in Group 2, but the difference was not statistically significant. During the 55-week follow-up, three courses of 18 daily home magnet therapy procedures each were performed. In both groups, starting from week 5 of the study, an improvement of pain on movement and at rest according to VAS compared to the baseline (p<0.01 at all assessment time points) was observed, which can be explained by a pronounced placebo effect, often observed in OA. The improvement of pain at rest was more prominent in Group 2 vs. Group 1 at Week 21 (p=0.038) and Week 55 (p=0.017) of the study, probably due to the anti-inflammatory effect. The overall WOMAC index score was also lower in Group 2 vs. Group 1 at Weeks 21 and 55 (p=0.03 at both time points). The mean articular cartilage thickness, determined by ultrasound, reduced in Group 1 and remained practically unchanged in Group 2 (p=0.011). No adverse events associated with the use of the ALMAG+ (Almag Active) device, according to the attending physician, and no exacerbations of immunoinflammatory rheumatic diseases during the study period were reported. The results of a double-blind, placebo-controlled study of magnet therapy using a portable device demonstrated analgesic, anti-inflammatory, and structure-modifying effects of this type of physiotherapeutic treatment. No adverse events and exacerbations of rheumatic diseases associated with the study treatment have been reported.

Correlation of Biomechanical Alterations under Gonarthritis between Overlying Menisci and Articular Cartilage

Just like menisci, articular cartilage is exposed to constant and varying stresses. Injuries to the meniscus are associated with the development of gonarthritis. Both the articular cartilage and the menisci are subject to structural changes under gonarthritis. The aim of this study was to investigate biomechanical alterations in articular cartilage and the menisci under gonarthritis by applying an indentation method. The study assessed 11 menisci from body donors as controls and 21 menisci from patients with severe gonarthritis. For the simultaneous examination of the articular cartilage and the menisci, we only tested the joint surfaces of the tibial plateau covered by the corresponding menisci. Over the posterior horn of the meniscus, the maximum applied load—the highest load registered by the load cell—of the arthritic samples of 0.02 ± 0.02 N was significantly greater (p = 0.04) than the maximum applied load of the arthritis-free samples of 0.01 ± 0.01 N. The instantaneous modulus (IM) at the center of the arthritic cartilage covered by the meniscus with 3.5 ± 2.02 MPa was significantly smaller than the IM of the arthritis-free samples with 5.17 ± 1.88 MPa (p = 0.04). No significant difference was found in the thickness of the meniscus-covered articular cartilage between the arthritic and arthritis-free samples. Significant correlations between the articular cartilage and the corresponding menisci were not observed at any point. In this study, the biomechanical changes associated with gonarthritis affected the posterior horn of the meniscus and the mid region of the meniscus-covered articular cartilage. The assessment of cartilage thickness as a structural characteristic of osteoarthritis may be misleading with regard to the interpretation of articular cartilage’s biomechanical properties.

Characterization and finite element validation of transchondral strain in the human hip during static and dynamic loading

Distribution of strain through the thickness of articular cartilage, or transchondral strain, is highly dependent on the geometry of the joint involved. Excessive transchondral strain can damage the solid matrix and ultimately lead to osteoarthritis. Currently, high-resolution transchondral strain distribution is unknown in the human hip. Thus, knowledge of transchondral strain patterns is of fundamental importance to interpreting the patterns of injury that occur in prearthritic hip joints. This study had three main objectives. We sought to 1) quantify high-resolution transchondral strain in the native human hip, 2) determine differences in transchondral strain between static and dynamic loading conditions to better understand recovery and repressurization of cartilage in the hip, and 3) create finite element (FE) models of the experimental testing to validate a modeling framework for future analysis. The transchondral strain patterns found in this study provide insight on the localization of strain within cartilage of the hip. Most notably, the chondrolabral junction experienced high tensile and shear strain across all samples, which explains clinical data reporting it as the most common region of damage in cartilage of the hip. Further, the representative FE framework was able to match the experimental static results and predict the dynamic results with very good agreement. This agreement provides confidence for both experimental and computational measurement methods and demonstrates that the specific anisotropic biphasic FE framework used in this study can both describe and predict the experimental results.

Thickness of the Stifle Joint Articular Cartilage in Different Large Animal Models of Cartilage Repair and Regeneration.

ObjectiveRegulatory guidelines for preclinical cartilage repair studies suggest large animal models (e.g., sheep, goat, [mini]-pig, or horse) to obtain results representative for humans. However, information about the 3-dimensional thickness of articular cartilage at different implantation sites in these models is limited.DesignTo identify the most suitable site for experimental surgery, cartilage thickness at the medial femoral condyle (MFC), lateral femoral condyle (LFC), and trochlea in ovine, caprine, and porcine cadaver stifle joints was systematically measured using hematoxylin-eosin staining of 6 µm paraffin sections and software-based image analysis.ResultsRegarding all ventral-dorsal regions of the MFC, goat showed the thickest articular cartilage (maximal mean thickness: 1299 µm), followed by sheep (1096 µm) and mini-pig (604 µm), with the highest values in the most ventral and dorsal regions. Also for the LFC, the most ventral regions showed the thickest cartilage in goat (maximal mean thickness: 1118 µm), followed by sheep (678 µm) and mini-pig (607 µm). Except for the mini-pig, however, the cartilage thickness on the LFC was consistently lower than that on the MFC. The 3 species also differed along the transversal measuring points on the MFC and LFC. In contrast, there were no consistent differences for the regional cartilage thickness of the trochlea among goat and sheep (≥780 µm) and mini-pig (≤500 µm).ConclusionsBased on their cartilage thickness, experimental defects on goat and sheep MFC may be viable options for preclinical cartilage repair studies, in addition to well-established horse models.

Lubricin Contributes to Homeostasis of Articular Cartilage by Modulating Differentiation of Superficial Zone Cells.

Lubricin encoded by the proteoglycan 4 (Prg4) gene is produced from superficial zone (SFZ) cells of articular cartilage and synoviocytes, which is indispensable for lubrication of joint surfaces. Loss-of-function of human and mouse Prg4 results in early-onset arthropathy accompanied by lost SFZ cells and hyperplastic synovium. Here, we focused on increases in the thickness of articular cartilage in Prg4-knockout joints and analyzed the underlying mechanisms. In the late stage of articular cartilage development, the articular cartilage was thickened at 2 to 4 weeks and the SFZ disappeared at 8 weeks in Prg4-knockout mice. Similar changes were observed in cultured Prg4-knockout femoral heads. Cell tracking showed that Prg4-knockout SFZ cells at 1 week of age expanded to deep layers after 1 week. In in vitro experiments, overexpression of Prg4 lacking a mucin-like domain suppressed differentiation of ATDC5 cells markedly, whereas pellets of Prg4-knockout SFZ cells showed enhanced differentiation. RNA sequencing identified matrix metalloproteinase 9 (Mmp9) as the top upregulated gene by Prg4 knockout. Mmp9 expressed in the SFZ was further induced in Prg4-knockout mice. The increased expression of Mmp9 by Prg4 knockout was canceled by IκB kinase (IKK) inhibitor treatment. Phosphorylation of Smad2 was also enhanced in Prg4-knockout cell pellets, which was canceled by the IKK inhibitor. Expression of Mmp9 and phosphorylated Smad2 during articular cartilage development was enhanced in Prg4-knockout joints. Lubricin contributes to homeostasis of articular cartilage by suppressing differentiation of SFZ cells, and the nuclear factor-kappa B-Mmp9-TGF-β pathway is probably responsible for the downstream action of lubricin. © 2020 American Society for Bone and Mineral Research (ASBMR).

Diagnostic Value of 3.0T MRI in Cartilage Injury Grading of Knee Osteoarthritis

Objective: At present, the grading diagnosis of knee osteoarthritis is mostly subjective evaluation, and lack of quantitative criteria, which brings some difficulty to diagnosis. To solve this problem, this study selected easily quantifiable indicators, such as cartilage thickness, cartilage volume and signal value, and analyzes their application value in grading diagnosis of cartilage injury by observing their change characteristics under MRI. Methods: Clinical data were collected from 54 patients with osteoarthritis of the knee (KOA) and 12 healthy volunteers, including 27 males and 39 females; age 38–63 years, with an average age of 47 ± 6.9 years. A total of 110 knee joints were tested, including 86 affected and 24 healthy joints. MRI data were collected, including patella, medial and lateral femoral condyle, medial and lateral tibial condyle, and for grading. The results were compared with those of arthroscopy to analyze the consistency of the two diagnostic methods. The 110 knee joints were divided into 5 groups according to the arthroscopic grading (0–IV grade), and compare the differences of cartilage thickness, cartilage volume and signal value under MRI among groups. Result: Among them, in terms of MRI grading, there were 15 cases of I grade, 21 cases of II grade, 26 cases of III grade, and 24 cases of IV grade. In terms of arthroscopy grading, there were 16 cases of I grade, 23 cases of II grade, 25 cases of III grade, and 22 cases of IV grade. The kappa value of the two diagnostic methods was 0.91, with high consistency (P &lt; 0.01). According to the results of arthroscopic grading diagnosis and analysis of the corresponding MRI data, it was found that the average thickness of normal articular cartilage in the patella, lateral tibia condyle, medial tibia condyle, lateral femur condyle, medial femur condyle is gradually thinning, and the thickness of articular cartilage in each part gradually thinned with the increase of injury grade. The difference between I grade and 0 grade was not statistically significant, and except for that, among other groups there were statistically significant (P &lt; 0.01); The volume of normal articular cartilage decreased from medial femoral condyle, lateral femoral condyle, patella, lateral tibial condyle and medial tibial condyle in turn, and the volume decreased gradually with the increase of injury grade. Except for the difference between I grade and 0 grade, there were statistical significance between other groups (P &lt; 0.01); signal value of normal articular cartilage decreased from medial tibial condyle, lateral femur condyle, medial femur condyle, lateral tibial condyle and patella in turn. Signal value increased with the increase of injury grade. Except for the difference between III grade and IV grade, there were statistical significance between other groups (P &lt; 0.01). Conclusion : MRI grading of cartilage injury in knee osteoarthritis is highly consistent with arthroscopy, with high accuracy. In MRI grading, reference to cartilage thickness, cartilage volume and signal value can effectively improve the diagnosis rate.

Effect of intraarticular injection of chondroitin sulfate into synovial joint elements in an experiment

Objective: to study morphological and morphometric changes in the epiphysis bone in a rat during the intra-articular injection of chondroitin sulfate (CS). Mаteriаl аnd methods. The object of the study was the knee joints of 36 Wistar rats. CS injections at a dose of 0.05 ml were performed once a week into one of the knee joints (experimental joint), and isotonic NaCl solution at the same volume was injected into the opposite joint (control joint). The animals in the number of 12 units were withdrawn from the experiment on the 7th, 14th, and 21st days, which corresponded to one week after one-, two-and three-fold intra-articular injections of HC and 0.9 % NaCl. The isolated knee joints were placed in a decalcifying liquid, then were fixed in 10% neutral buffered formalin. 4 micron histological sections were stained with hematoxylin and eosin. The morphometric analysis assessed the thickness of hyaline articular cartilage, the thickness of the epiphysis growth zone cartilage, and the cell content of the subchondral bone. Results. The study of the thickness of the articular cartilage, the growth zone of epiphyseal cartilage and the cellular composition of the subchondral bone has showed a statistically significant dynamic increase in these indicators after the 2nd and 3rd intra-articular injections of CS. The assessment of the thickness of the articular cartilage on the 21st day found some statistically significant differences between the experimental and control groups (p &lt; 0.0001), the thickness of the epiphyseal cartilage had increased significantly by that time (p &lt; 0.0001), and the cell content of bone marrow showed statistically significant differences (p = 0.002). Conclusion. The obtained data testify to a pronounced regenerative effect of CS, injected intra-articularly into articular cartilage.

Laboratory and instrumental study of knee joints in patients&#x0D; with early gonarthrosis: search for relationship

Aimwas to identify features of subchondral bone remodeling and synovitis severity in patients with early knee osteoarthritis using laboratory and instrumental methods.&#x0D; Materials and methods.The study covered 60 patients with I-II radiological stages (by J. Kellgren and J. Lawrence, 1952) of gonarthrosis (according to R.D. Altman, 1991). Complex of clinical (history, complaints, palpation of joints, pain assessment by Visual Analogue Scale [VAS]), laboratory (interleukin-6, osteocalcin, Beta-Cross Laps, C-reactive protein [CRP] and others) and instrumental (X-ray, ultrasonography of knee joints) examinations of patients was carried out with subsequent statistical data processing.&#x0D; Results.In patients with stage II gonarthrosis, Beta-Cross Laps, CRP levels, osteophyte size were significantly higher, and articular cartilage thickness was lower in comparison with stage I group. Correlations were found between: pain intensity according to VAS and volume of upper torsion of knee joint; interleukin-6 and osteophyte size, volume of upper torsion, Beta-Cross Laps; level of Beta-Cross Laps and osteocalcin, osteophyte size; and some other relationships.&#x0D; Conclusion. In patients with I-II radiological stages of gonarthrosis, remodeling of subchondral bone is observed and accompanied by tissue turnover changes that it is could be used in targeted therapy. Serum Beta-Cross Laps is important marker for early progression of gonarthrosis.

Kartogenin mediates cartilage regeneration by stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells

A decrease in the number of endogenous stem cells in cartilage is regarded as the cause of cartilage degeneration. Kartogenin (KGN) is known to induce chondrogenesis of cartilage stem/progenitor cells (CSPCs). Using CSPCs isolated from rat cartilage, we analysed changes in the transcriptome after treatment with KGN in vitro. An animal model of destabilization of the medial meniscus (DMM) was then used to identify the effect of intra-articular (IA) KGN injection on CSPC proliferation in vivo. Here, we demonstrated that KGN promoted the proliferation of CSPCs isolated from cartilage. The percentage of G2-M phase cells in the KGN-treated group reached over 10%, nearly twice that in the control group. Transcriptomic profiling of rat CSPCs revealed significant changes in KGN-treated samples compared to control samples. The gene expression levels of IL-6 and its coreceptor Gp130 were much higher in the KGN-treated group than in the control group. Phosphorylation of the IL-6 downstream molecule Stat3 was enhanced via KGN stimulation. The DMM animal model showed increased articular cartilage thickness after IA KGN injection. IHC staining also demonstrated upregulation of Stat3 phosphorylation and enhanced distribution of CD44+/CD105+ cells in cartilage following IA KGN injection. Thus, our data suggested that KGN promoted cartilage regeneration at least partially by stimulating IL-6/Stat3-dependent proliferation.

Sonographic assessment of femoral cartilage thickness in healthy adults.

ObjectiveThis study was performed to obtain normative data of the distal femoral cartilage thickness in healthy adults by ultrasound.MethodsThis cross-sectional study included 72 healthy adults. The demographic characteristics of the participants were recorded, and the thickness of the femoral articular cartilage was measured using a 5- to 18-MHz linear probe.ResultsSignificant statistical difference towards the male side at left medial condyle (P = 0.001) and left lateral condyle (P = 0.009). Weakly positive statistical difference was noted towards the male side at right medial condyle (P = 0.06) and right lateral condyle (P = 0.07). The femoral cartilage thickness in the study participants did not correlate with weight, body mass index, and age (P >0.05). Positive statistical correlation with height noted in right medial condyle, right lateral condyle, right intercondylar area, and left medial condyle.ConclusionThis study increases the pool of normative data of femoral cartilage thickness measurements. Additionally, the findings of this study emphasize the fact that women have thinner cartilage than men in four of the studied parameters.

An experimentally induced osteoarthritis model in horses performed on both metacarpophalangeal and metatarsophalangeal joints: Technical, clinical, imaging, biochemical, macroscopic and microscopic characterization.

Osteoarthritis is a common cause of pain and economic loss in both humans and horses. The horse is recognized as a suitable model for human osteoarthritis, because the thickness, structure, and mechanical properties of equine articular cartilage are highly comparable to those of humans. Although a number of equine experimental osteoarthritis models have been described in the literature, these cases generally involve the induction of osteoarthritis in just one joint of each animal. This approach necessitates the involvement of large numbers of horses to obtain reliable data and thus limits the use of this animal model, for both economic and ethical reasons. This study adapts an established equine model of post-traumatic osteoarthritis to induce osteoarthritis-associated lesions in all 4 fetlock joints of the same horse in order to reduce the number of animals involved and avoid individual variability, thus obtaining a more reliable method to evaluate treatment efficacy in future studies. The objectives are to assess the feasibility of the procedure, evaluate variability of the lesions according to interindividual and operated-limb position and describe the spontaneous evolution of osteoarthritis-associated pathological changes over a twelve-week period. The procedure was well tolerated by all 8 experimental horses and successfully induced mild osteoarthritis-associated changes in the four fetlock joints of each horse. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analyses of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints. No significant differences were found in the progression of osteoarthritis-associated changes between horses or between the different limbs, with the exception of higher synovial effusion in hind fetlocks compared to front fetlocks and higher radiographic scores for left fetlocks compared to the right. This model thus appears to be a reliable means to evaluate the efficacy of new treatments in horses, and may be of interest for translational studies in human medicine.

Reliability of a Novel Semiautomated Ultrasound Segmentation Technique for Assessing Average Regional Femoral Articular Cartilage Thickness

Ultrasound imaging is a clinically feasible tool to assess femoral articular cartilage and may have utility in tracking early knee osteoarthritis development. Traditional assessment techniques focus on measurements at a single location, which can be challenging to adopt for novice raters. To introduce a novel semiautomated ultrasound segmentation technique and determine the intrarater and interrater reliability of average regional femoral articular cartilage thickness and echo intensity of a novice and expert rater. Descriptive observational study. Orthopedic clinic. Fifteen participants (mean [SD]; age 23.5 [4.6]y, height = 172.6 [9.3]cm, mass = 79.8 [15.7]kg) with a unilateral history of anterior cruciate ligament reconstruction participated. None. One rater captured anterior femoral cartilage images of the participants' contralateral knees using a transverse suprapatellar ultrasound assessment. The total femoral cartilage cross-sectional area of each image was segmented by a novice and expert rater. A novel custom program automatically separated the cartilage segmentations into medial, lateral, and intercondylar regions to determine the cross-sectional area and cartilage length. The average cartilage thickness in each region was calculated by dividing the cross-sectional area by the cartilage length. Echo intensity was calculated as the average gray-scale pixel value of each region. Two-way random effect intraclass correlations coefficient (ICC) for absolute agreement were used to determine the interrater reliability between a novice and expert rater, as well as the intrarater reliability of the novice rater. The novice rater demonstrated excellent intrarater (ICC [2,k] range = .993-.997) and interrater (ICC [2,k] range = .944-.991) reliability with the expert rater of all femoral articular cartilage average thickness and echo intensity regions. The novel semiautomated average cartilage thickness and echo-intensity assessment is efficient, systematic, and reliable between an expert and novice rater with minimal training.

Evaluation of musculoskeletal phenotype of the G608G progeria mouse model with lonafarnib, pravastatin, and zoledronic acid as treatment groups

Hutchinson-Gilford progeria syndrome (HGPS) is a uniformly fatal condition that is especially prevalent in skin, cardiovascular, and musculoskeletal systems. A wide gap exists between our knowledge of the disease and a promising treatment or cure. The aim of this study was to first characterize the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and to determine the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. Microcomputed tomography and CT-based rigidity analyses were performed to assess cortical and trabecular bone structure, density, and rigidity. Bones were loaded to failure with three-point bending to assess strength. Contrast-enhanced µCT imaging of mouse femurs was performed to measure glycosaminoglycan content, thickness, and volume of the femoral head articular cartilage. Advanced glycation end products were assessed with a fluorometric assay. The changes demonstrated in the cortical bone structure, rigidity, stiffness, and modulus of the HGPS G608G mouse model may increase the risk for bending and deformation, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this HGPS model resemble changes observed in the age-matched WT controls, including early loss of glycosaminoglycans, and decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases in the elderly. Lonafarnib monotherapy did not improve bone or cartilage parameters, but treatment combinations with pravastatin and zoledronic acid significantly improved bone structure and mechanical properties and cartilage structural parameters, which ameliorate the musculoskeletal phenotype of the disease.

A review on segmentation of knee articular cartilage: from conventional methods towards deep learning.

In this paper, we review the state-of-the-art approaches for knee articular cartilage segmentation from conventional techniques to deep learning (DL) based techniques. Knee articular cartilage segmentation on magnetic resonance (MR) images is of great importance in early diagnosis of osteoarthritis (OA). Besides, segmentation allows estimating the articular cartilage loss rate which is utilised in clinical practice for assessing the disease progression and morphological changes. It has been traditionally applied in quantifying longitudinal knee OA progression pattern to detect and assess the articular cartilage thickness and volume. Topics covered include various image processing algorithms and major features of different segmentation techniques, feature computations and the performance evaluation metrics. This paper is intended to provide researchers with a broad overview of the currently existing methods in the field, as well as to highlight the shortcomings and potential considerations in the application at clinical practice. The survey showed that state-of-the-art techniques based on DL outperform the other segmentation methods. The analysis of the existing methods reveals that integration of DL-based algorithms with other traditional model-based approaches has achieved the best results (mean Dice similarity coefficient (DSC) between 85.8% and 90%).

Changes in medial compartment loading and articular cartilage thickness 24 months after limb realignment surgery in the operative and non-operative limbs

Purpose: High tibial osteotomy (HTO) is a limb realignment surgery for patients with medial compartment knee osteoarthritis (OA) and varus alignment. The surgery is proposed to improve aberrant knee joint loading and thereby alter disease progression. The purpose of the present study was to quantify and compare changes in MRI-based measures of medial articular cartilage thickness and 3D gait analysis-based measures of medial-to-lateral knee load distribution preoperatively, and at 12 and 24 months postoperatively in both the operative and non-operative limbs.

ARTICULAR CARTILAGE THICKNESS IN PEDIATRIC AND ADOLESCENT KNEES DECREASES WITH AGE AND SKELETAL MATURITY: IMPLICATIONS FOR OSTEOCHONDRAL GRAFTING PROCEDURES

Background:Quantifying native cartilage thickness in pediatric and adolescent knees can help match donor and recipient sites for articular cartilage restoration procedures such as osteochondral autograft transplantation (OATS) and osteochondral allograft transplantation (OCA).Hypothesis/Purpose:The purpose of the current study was to quantify articular cartilage thickness in pediatric and adolescent knees using magnetic resonance imaging (MRI). We hypothesized that cartilage thickness is inversely correlated with skeletal maturity and age.Methods:One hundred and twenty MRI scans were evaluated in a cohort of patients 9 to 18 years old without osteochondral lesions, chondral wear or pathology, intraarticular fractures, history of knee surgery, or inflammatory arthropathy. Measurements of articular cartilage thickness at the medial femoral condyle, lateral femoral condyle, lateral trochlea, and patella were made on axial, coronal, and sagittal MRI scans (Figure 1). Skeletal maturity was categorized as ‘open’, ‘closing’, or ‘closed’ based on the status of the proximal tibial and distal femoral growth plates. Descriptive statistics was used to evaluate cartilage thickness by age and sex. Independent samples t-test, analysis of variance (ANOVA), and linear regression were performed to investigate for associations with sex, skeletal maturity, and age.Results:On the femur, cartilage was thickest at the lateral trochlea with mean articular thickness of 4.2 ± 1.4 mm in males and 3.6 ± 1.3 mm in females (p=0.015) (Table 1). Skeletally immature patients with open physes had significantly thicker cartilage at the medial femoral condyle, lateral femoral condyle, and lateral trochlea compared to patients with closing and closed physes (Figure 2). Linear regression analysis also revealed a significant association between femoral cartilage thickness and age (Figure 3). Age explained 63% of the variance at the medial femoral condyle (B=6.1, p<0.001), 64% of the variance at the lateral femoral condyle (B=4.9, p<0.001), and 68% of the variance at the lateral trochlea (B=8.2, p<0.001) (Table 2). In contrast, cartilage thickness at the patella did not significantly vary by age, sex, or skeletal maturity (Figures 2 and 4).Conclusion:There is a strong inverse association between increasing age and cartilage thickness of the femoral condyles and lateral trochlea. In particular, pediatric knees demonstrate relatively thick cartilage at the lateral trochlea that decreases with age. This information will help surgeons understand recipient site anatomy and identify appropriate donor site tissue for articular cartilage restoration procedures such as OATS and OCA in children and adolescents.Tables:Table 1.Mean articular cartilage thickness of the femur and patellaCombined (n=120)Male(n=40)Female(n=60) p valueMedial femoral condyle3.2 ± 1.03.5 ± 1.02.9 ± 0.80.001Lateral femoral condyle2.8 ± 0.72.9 ± 0.72.7 ± 0.70.056Lateral trochlea3.9 ± 1.44.2 ± 1.43.6 ± 1.30.015Median ridge of patella4.2 ± 0.94.4 ± 0.94.1 ± 0.90.080Medial facet of patella4.7 ± 1.04.8 ± 1.04.6 ± 0.90.320Lateral facet of patella4.6 ± 0.84.7 ± 0.84.5 ± 0.80.185Table 2.Linear regression of articular cartilage thickness of the femur and patella by ageR2 B p valueMedial femoral condyle0.636.1<0.001Lateral femoral condyle0.644.9<0.001Lateral trochlea0.688.2<0.001Median ridge of patella0.024.80.090Medial facet of patella0.045.50.032Lateral facet of patella0.0014.50.741Figures:Figure 1.Measurements of patellofemoral articular cartilage thickness Measurements of articular cartilage thickness were made on (A) coronal, (B, C) sagittal, and (D) axial magnetic resonance imaging (MRI) of the knee. For the medial femoral condyle, cartilage thickness was measured at five regions: midpoint of the medial condyle (MFC) and midpoints of Cahill zones 1 (MID1), 2 (MID2), B (MIDB) and C (MIDC). Similarly, measurements of cartilage thickness of the lateral femoral condyle were made at the midpoint of the lateral condyle (LFC) and midpoints of Cahill zones 4 (MID4), 5 (MID5), B (MIDB), and C (MIDC). Measurement of the lateral trochlea was made at midpoint of Cahill zone A (MIDA). Measurements on the patella were made at the midpoint of the medial facet (MF), midpoint of the lateral facet (LF), and the median ridge (MR) on axial and sagittal MRI scans. Figure 2.Mean articular cartilage thickness of the femur and patella by growth plate statusFigure 3.Mean articular cartilage thickness of the femur by ageFigure 4.Mean articular cartilage thickness of the patella by age

Ultrasonographic measurement of femoral cartilage thickness in type II diabetic patients.

The aim of this study is to compare the distal femoral cartilage thickness of patients with type II diabetes mellitus with those of healthy subjects using ultrasonography. The study comprised 34 patients and 36 healthy subjects. Demographic characteristics of all the participants were recorded. The thickness of the femoral articular cartilage was measured using a 5-18MHzlinearprobe.Measurements were performed bilaterally from three points (intercondylar area, medial condyle, and lateral condyle). No significant difference could be found between patients and healthy subjects. Two demographic characteristics correlated positively with diabetic patients.

Kappa opioids modulate hedgehog signaling to attenuate osteoarthritis

Purpose: Osteoarthritis (OA) affects 50 million Americans, at an annual cost of $100 billion. Pain management is currently a hallmark of OA treatment. One of the most frequently employed treatment strategies involves opioid analgesics. Opioids are highly addictive and have led to an opioid epidemic. One strategy to reduce opioid addiction is to implement kappa-opioid receptor (KOR) agonist medications which have been documented to provide pain-relief without the addictive potential of commonly used opioid medications (which target the mu-opioid receptor). Our previous work showed that KOR is expressed in chondrocytes and synovial cells. Previous studies have also shown that inhibition of the Hedgehog (Hh) signaling pathway prevents cartilage degeneration and promotes repair in animal models of OA. Current study was designed to explore if modulation of kappa opioid receptor (KOR) signaling may have a therapeutic potential for achieving disease-modifying activity in OA models through Hh modulation. Methods: Normal human primary tissues were obtained from the National Disease Research Interchange (NDRI). Human OA samples were collected from patients with severe osteoarthritis undergoing total joint replacements. Normal porcine articular cartilage tissue was used for explant studies. For in vivo studies a partial medial meniscectomy (PMM) rat model was used. A novel automated 3D indentation mapping mechanical tester (Mach-1) was used to quantify articular cartilage thickness and stiffness properties. Results: We have demonstrated that activation of KOR by a selective peptide agonist JT09 inhibits Hh signaling in normal and osteoarthritic human chondrocytes via cAMP/CREB pathway. JT09 has also markedly decreased matrix degeneration in porcine explants induced by a Hh agonist SAG. Moreover, in vivo application of JT09 via intra-articular injection significantly attenuated rat articular cartilage degeneration after PMM. In JT09 treated rats, cartilage content and structure were largely maintained, and osteophyte formation was greatly reduced. In addition, treatment with JT09 prevented functional compressive tissue degeneration following PMM. Conclusions: Current study defines a novel molecular mechanism for the role of the KOR in articular cartilage homeostasis and disease, providing a potential unifying mechanistic basis for the overlap in processes and pathologies shown to involve opioid and Hh signaling. Moreover, this study identifies a potential novel therapeutic strategy in which KOR modulation in cartilage and/or synovial tissue can improve outcomes in patients with arthritis.

Wnt16 Overexpression in Osteoblasts Increases the Subchondral Bone Mass but has no Impact on Osteoarthritis in Young Adult Female Mice

Epidemiological studies have shown that high bone mineral density (BMD) is associated with an increased risk of osteoarthritis (OA), but the causality of this relationship remains unclear. Both bone mass and OA have been associated with the WNT signaling pathway in genetic studies, there is thus an interest in studying molecular partners of the WNT signaling pathway and OA. Female mice overexpressing WNT16 in osteoblasts (Obl-Wnt16 mice) have an increased bone mass. We aimed to evaluate if the high bone mass in Obl-Wnt16 mice leads to a more severe experimental OA development than in WT control mice. We induced experimental OA in female Obl-Wnt16 and WT control mice by destabilizing the medial meniscus (DMM). The Obl-Wnt16 mice displayed thicker medial and lateral subchondral bone plates as well as increased subchondral trabecular bone volume/tissue volume (BV/TV) but un-altered thickness of articular cartilage compared to WT mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the Obl-Wnt16 and WT mice. Both the Obl-Wnt16 and WT mice developed osteophytes in the DMM-operated tibia to a similar extent. We conclude that although the Obl-Wnt16 female mice have a high subchondral bone mass due to increased WNT signaling, they do not exhibit a more severe OA phenotype than their WT controls. This demonstrates that high bone mass does not result in an increased risk of OA per se.

Changes in Cartilage and Subchondral Bone of Femoral Trochlear Groove After Patellectomy in Growing Rabbits.

ObjectiveTo explore the effects of patellectomy on the bony and cartilaginous morphology of the trochlear groove in growing rabbits.MethodsForty‐eight 4‐week‐old New Zealand white rabbits were randomly assigned to two groups. The control group underwent a sham surgical procedure, whereas the patellectomy group underwent patella excision surgery. Half of the rabbits in each group were sacrificed 3 months postoperatively; the rest were sacrificed 6 months postoperatively. Hematoxylin and eosin staining was performed on collected samples. Measurements included the bony and cartilaginous sulcus angles of the trochlear groove. In addition, the thickness of the articular cartilage at the deepest sulcus position (central thickness) and at the mid‐position of the medial and lateral facets was measured and compared between groups.ResultsThree months after surgery, histological images revealed significant differences between the control group and the patellectomy group in cartilaginous sulcus angle (144.2° ± 1.5° vs 151.9° ± 2.4°, respectively; P < 0.001). No obvious difference in bony sulcus angle was found between the groups. Six months after surgery, significant between‐group differences were observed in cartilaginous sulcus angle (136.3° ± 2.5° in control group vs 160.7° ± 3.0° in patellectomy group, P < 0.001) and bony sulcus angle (136.2° ± 2.2° in control group vs 160.4° ± 2.6° in patellectomy group, P < 0.001). However, there were no significant intra‐group differences between cartilaginous and bony sulcus angles in either group. Three months after surgery, significant between‐group differences were detected in articular cartilage thickness at the three different positions (medial facet: 324.3 ± 14.0 μm in control group vs 391.7 ± 98.8 μm in patellectomy group, P = 0.029; central position: 362.1 ± 13.6 μm in control group vs 730.3 ± 76.8 μm in patellectomy group, P < 0.001; lateral facet: 324.6 ± 12.7 μm in control group vs 358.5 ± 38.7 μm in patellectomy group, P = 0.009). No between‐group differences in cartilage thickness were found at 6 months.ConclusionsAbnormal mechanical stress (patellectomy) during a rabbit's development can cause flattening of the femoral trochlear cartilage, followed by changes in the subchondral osseous layer. Abnormal mechanical stress is a crucial factor in the development of trochlear groove dysplasia.