Articular Cartilage In Patients Research Articles

Three-Dimensional Printing of Models of Patellofemoral Joint Articular Cartilage in Patients With Patella Instability for Observing Joint Congruity

Three-dimensional (3D) modeling and printing are increasingly used in the field of orthopaedic surgery for both research and patient care. One area where they are particularly helpful is in improving our understanding of the patellofemoral (PF) joint. Heretofore, morphological studies that use 3D models of the PF joint have primarily been based on computed tomography imaging data and thus do not incorporate articular cartilage. Here, we describe a method for creating 3D models of the articular surfaces of the PF joint based on magnetic resonance imaging. Models created using this technique can be used to improve our understanding of the morphology of the articular surfaces of the PF joint and its relationship to joint pathologies. Of particular interest is our finding of articular congruity in printed articular cartilage surfaces of dysplastic PF joints of recurrent patella dislocators.

Global, but not chondrocyte-specific, MT1-MMP deficiency in adult mice causes inflammatory arthritis

Membrane-type I metalloproteinase (MT1-MMP/MMP14) plays a key role in various pathophysiological processes, indicating an unaddressed need for a targeted therapeutic approach. However, mice genetically deficient in Mmp14 show severe defects in development and growth. To investigate the possibility of MT1-MMP inhibition as a safe treatment in adults, we generated global Mmp14 tamoxifen-induced conditional knockout (Mmp14kd) mice and found that MT1-MMP deficiency in adult mice resulted in severe inflammatory arthritis. Mmp14kd mice started to show noticeably swollen joints two weeks after tamoxifen administration, which progressed rapidly. Mmp14kd mice reached a humane endpoint 6 to 8 weeks after tamoxifen administration due to severe arthritis. Plasma TNF-α levels were also significantly increased in Mmp14kd mice. Detailed analysis revealed chondrocyte hypertrophy, synovial fibrosis, and subchondral bone remodeling in the joints of Mmp14kd mice. However, global conditional knockout of MT1-MMP in adult mice did not affect body weight, blood glucose, or plasma cholesterol and triglyceride levels. Furthermore, we observed substantial expression of MT1-MMP in the articular cartilage of patients with osteoarthritis. We then developed chondrocyte-specific Mmp14 tamoxifen-induced conditional knockout (Mmp14chkd) mice. Chondrocyte MT1-MMP deficiency in adult mice also caused apparent chondrocyte hypertrophy. However, Mmp14chkd mice did not exhibit synovial hyperplasia or noticeable arthritis, suggesting that chondrocyte MT1-MMP is not solely responsible for the onset of severe arthritis observed in Mmp14kd mice. Our findings also suggest that highly cell-type specific inhibition of MT1-MMP is required for its potential therapeutic use.

Iron regulates chondrocyte phenotype in haemophilic cartilage through the PTEN/PI3 K/AKT/FOXO1 pathway

ABSTRACTObjectiveOur previous study demonstrated that iron overload could lead to haemophilic cartilage destruction by changing chondrocyte phenotype. This change was caused by iron’s effect on chondrocyte expression of FGF23 and SOX9, in addition to iron-induced chondrocyte apoptosis and cartilage extracellular matrix degradation. However, the underlying mechanisms remain unclear. This study aimed to determine the mechanism by which iron influences chondrocyte phenotype in the pathogenesis of haemophilic cartilage destruction.MethodsThe expression of the PTEN/PI3K/AKT/FOXO1 signal pathway in the articular cartilage of patients with haemophilic arthritis (HA) or osteoarthritis (OA) was determined using western blot (WB). Additionally, we quantified the expression of iron-induced PTEN, PI3K, p-PI3K, AKT, p-AKT, FOXO1, and p-FOXO1 in primary human normal chondrocyte cells (HUM-iCell-s018) using WB.ResultsWe found that compared to that in patients with OA, the expression of PTEN, PI3K, AKT, and FOXO1 in the articular cartilage of patients with HA was up-regulated, while the expression of p-PI3K, p-AKT, and p-FOXO1 was down-regulated. Additionally, iron increased the expression of PTEN, PI3K, AKT, and FOXO1 and suppressed that of p-PI3K, p-AKT, and p-FOXO1 in chondrocytes in a dose-dependent manner.ConclusionsOur findings demonstrated that iron was involved in the pathogenesis of haemophilic cartilage destruction by affecting chondrocyte phenotype through the inhibition of the PTEN/PI3K/AKT/FOXO1 pathway.

Timing of anterior cruciate ligament reconstruction and its effect on associated chondral damage and meniscal injury: a prospective observational study

Background: Following an anterior cruciate ligament (ACL) tear, associated injuries in the knee involving menisci and articular cartilage increase with time. This study was performed to assess the distribution of secondary injuries after an ACL tear with time and identify a suitable timing for the reconstruction surgery. Methods: 74 patients with an ACL tear were divided into three groups based on time since injury- less than six months, six months to one year, and greater than one year. The odds of finding each lesion in every group were calculated and tested for statistical significance. Receiver operating characteristic curves (ROC) were drawn to predict individual lesions with time since injury. The diagnostic performance and statistical significance of these tests were identified. Results: The odds of finding all lesions were greater than one after a year of ACL tear but only chondral damage was statistically significant (p=0.025). Poor diagnostic accuracy was observed for medial meniscal injury even after three years of an ACL tear. Chondral injury showed a good area under the curve (0.817) which predicted chondral damage with a sensitivity of 62% at a cut-off of three years after the ACL injury. Conclusions: After three years of ACL tear, meniscal injuries could not be accurately predicted. However, a significant rise in chondral injuries could be seen and predicted accurately with good sensitivity. There could be a role of MRI or arthroscopy to assess the extent of injury of articular cartilage in patients who do not undergo ACL reconstruction after this time.

Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling.

Dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) signaling is involved in the dynamic balance of catabolism and anabolism in articular chondrocytes. This study aimed to investigate the roles and mechanism of DYRK1A in the pathogenesis of osteoarthritis (OA). The expressions of DYRK1A and its downstream signal epidermal growth factor receptor (EGFR) were detected in the cartilage of adult wild-type mice with destabilized medial meniscus (DMM) and articular cartilage of patients with OA. We measured the progression of osteoarthritis in chondrocyte-specific knockout DYRK1A(DYRK1A-cKO) mice after DMM surgery. Knee cartilage was histologically scored and assessed the effects of DYRK1A deletion on chondrocyte catabolism and anabolism. The effect of inhibiting EGFR signaling in chondrocytes from DYRK1A-cKO mice was analyzed. Trauma-induced OA mice and OA patients showed downregulation of DYRK1A and EGFR signaling pathways. Conditional DYRK1A deletion aggravates DMM-induced cartilage degeneration, reduces the thickness of the superficial cartilage, and increases the number of hypertrophic chondrocytes. The expression of collagen type II, p-ERK, and aggrecan was also downregulated, and the expression of collagen type X was upregulated in the articular cartilage of these mice. Our findings suggest that DYRK1A delays the progression of knee osteoarthritis in mice, at least in part, by maintaining EGFR-ERK signaling in articular chondrocytes.

Quantitative T2 mapping magnetic resonance imaging of articular cartilage in patients with juvenile idiopathic arthritis

PurposeWe aimed to analyze the microstructure changes of knee cartilage in Juvenile idiopathic arthritis (JIA) patients with active synovitis using quantitative magnetic resonance imaging (MRI) T2 mapping technique. Materials and methodsThis study included 23 JIA patients, who underwent bilateral knee joints by using a MR imaging protocol with the addition of a coronal T2 mapping. The femorotibial joint cartilage of participants was divided into eight subregions. Twenty-four (52.17%) of 46 joints (non-synovitis group), and twenty-two (47.83%) joint cases (active-synovitis group) were respectively calculated the T2 mean values for each subregion. Student’s T test or Mann–Whitney U test was used to determine the statistical differences of each subregion in the non-synovitis and active-synovitis groups, which is also applied to define the distribution differences of cartilage subregion in femoral and tibial. ResultsThe T2 mean values of the superficial and deep zone of cartilage for active synovitis group were respectively higher than those for non-synovitis group (P < 0.05), except for the deep zone of cartilage in lateral tibial plateau (LTP) (P > 0.05). The mean T2 values of the deep zone in femoral cartilage for active synovitis group were significantly higher than that of tibial (P < 0.05). ConclusionThe finding of an increased average T2 values in active synovitis for JIA patients, especially in the deep cartilage of femoral condyle, which suggests that T2 values may reflect cartilage microstructure differences that occur in JIA. T2 mapping as an objective and quantitative method may allow for early detection of cartilage changes.

Generation of human immortalized chondrocytes from osteoarthritic and healthy cartilage

After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine.Cite this article: Bone Joint Res2023;12(1):46-57.

Expression of CILP-2 and DDR2 and ultrastructural changes in the articular cartilage of patients with knee osteoarthritis undergoing total knee arthroplasty: a pilot morphological study.

The aim of the study was to correlate the immunohistochemical expression of cartilage intermediate layer protein 2 (CILP-2) and discoidin domain receptor 2 (DDR2), and the ultrastructural changes in the cartilage with the degree of articular cartilage damage in osteoarthritis (OA) patients. Cartilage samples were obtained from twenty patients aged from 46 to 68years undergoing total knee arthroplasty. In each patient, medial and lateral tibial plateau samples were analysed applying OARSI histopathology grading. Positive correlation was noted between the extent of CILP-2 staining intensity and OARSI grades. Abundant staining for CILP-2 was found in the superficial and middle layers and in the pericellular matrix (PCM) of the deep zone. Transmission electron microscopy studies demonstrated strong damage of chondrocytes, the organelles were often diminished or focally aggregated. As a characteristic finding, PCM was frequently expanded, which may reflect a pathogenic step in OA progression. In conclusion, CILP-2 may potentially be a relevant marker of OA progression as its expression correlated better with cartilage damage than the known marker of articular cartilage damage, DDR2.

FGF23 and SOX9 expression in haemophilic cartilage: In vitro studies of the effects of iron.

Clarifying the links between iron and FGF23, SOX9 expression in chondrocytes would be helpful for comprehending articular cartilage degradation pathogenesis in blood-induced arthritis and exploring new protective methods. The purpose of this study was to determine iron regulation of fibroblast growth factor 23 (FGF23) and SRY-box 9 (SOX9) in human chondrocytes, an area which is unexplored in blood-induced arthritis cartilage degradation pathogenesis. Expression of FGF23, SOX9, MMP13 and collagen Ⅱ in articular cartilage of patients with osteoarthritis (OA) or haemophilic arthritis (HA) was determined by western blot (WB). Iron-induced FGF23 and SOX9 mRNA and protein expression in primary human normal chondrocyte cells (HUM-iCell-s018) was quantified by qRT-PCR and WB, respectively. We found that compared with OA patients, the expression of FGF23, MMP13 in articular cartilage of patients with HA was up-regulated, while the expression of SOX9, collagen Ⅱ was down-regulated. Iron-induced FGF23 and suppressed SOX9 expression in chondrocytes in a dose-dependent manner. These findings demonstrated that iron was involved in hemophilic cartilage lesion directly via changing cartilage phenotype through regulation of FGF23 and SOX9 expression in chondrocytes.

Three-Dimensional Reconstruction Algorithm-Based Magnetic Resonance Imaging Evaluation of Biomechanical Changes in Articular Cartilage in Patients after Anterior Cruciate Ligament Reconstruction.

This study aimed to investigate the evaluation of biomechanical changes in articular cartilage in patients after anterior cruciate ligament (ACL) reconstruction by magnetic resonance imaging (MRI) based on a three-dimensional (3D) finite element model. The data of 90 patients undergoing arthroscopic ACL reconstruction in the hospital were collected and divided into the stable group (54 cases) and the unstable group (36 cases). A load of up to 134N was applied to the 3D finite element model, and the kinematics of knee flexion at 0°, 30°, 60°, and 90° were examined. The tibial anteversion, tibial rotation, and ACL/graft tension were recorded in the 3D finite element model, which was randomly divided into the normal group (intact group, n = 30), the ACL rupture group (deficient group, n = 30), and the anatomical reconstruction group (anatomical group, n = 30). When the graft was fixed at 0°, the anterior tibial translation at 30°, 60°, and 90° in the anatomic group was 8–19% higher than the normal value under 134 N anterior load. The tibial internal rotation in the anatomic group was 18% and 28% higher than the normal value at 30° and 90°. When the graft was fixed at 30°, the anterior tibial translation at 60° and 90° of the anatomic group was 15% higher than the normal value. The tibial internal rotation at 90° of the anatomic group was 16% higher than the normal value, and the above differences had statistical significance (P < 0.05). MRI images were used to assess the bone tunnel angle, and the statistical analysis by the independent-samples t-test showed that there were significant differences in the bone tunnel angle between the stable group and the unstable group (P < 0.05). Currently, based on the 3D finite element model, MRI can accurately evaluate the postoperative effect of anatomical ACL reconstruction in the position, diameter, and angle of tibial and femoral bone tunnels, which can be applied to clinical promotion.

Differential regulation of the water channel protein aquaporins in chondrocytes of human knee articular cartilage by aging

Knee cartilage is in an aqueous environment filled with synovial fluid consisting of water, various nutrients, and ions to maintain chondrocyte homeostasis. Aquaporins (AQPs) are water channel proteins that play an important role in water exchange in cells, and AQP1, -3, and -4 are known to be expressed predominantly in cartilage. We evaluated the changes in AQP expression in chondrocytes from human knee articular cartilage in patients of different ages and identified the key factor(s) that mediate age-induced alteration in AQP expression. The mRNA and protein expression of AQP1, -3 and -4 were significantly decreased in fibrocartilage compared to hyaline cartilage and in articular cartilage from older osteoarthritis patients compared to that from young patients. Gene and protein expression of AQP1, -3 and -4 were altered during the chondrogenic differentiation of C3H10T1/2 cells. The causative factors for age-associated decrease in AQP included H2O2, TNFα, and HMGB1 for AQP1, -3, and -4, respectively. In particular, the protective effect of AQP4 reduction following HMGB1 neutralization was noteworthy. The identification of other potent molecules that regulate AQP expression represents a promising therapeutic approach to suppress cartilage degeneration during aging.

Osteochondral Lesions of the Talus: Factors Predictive of Cartilage Integrity

Objectives:The integrity of articular cartilage in patients with osteochondral lesions of the talus (OLTs) guides treatment. The ability to predict cartilage integrity in OLTs, as previously published for OCD of the knee, would be beneficial. The purpose of this study is to evaluate the association of radiographic and MRI findings and articular cartilage integrity at the time of ankle arthroscopy for OLTs.Methods:A single-institution retrospective review identified patients 19 years of age and younger with operative treatment of OLTs from 2010 – 2017. Demographics and intra-operative findings at the time of ankle arthroscopy were identified by chart review. Radiographs were assessed for physeal status, OLT location, and Berndt and Hardy grade. MRIs were reviewed for OLT size and location, modified Kramer grade, and cartilage status.Results:53 patients with 54 OLTs and a mean age of 13.6 years (range 7 – 19 years) were included. Radiographic details are listed in Table 1. OLTs were located in the posteromedial talus in 39 patients (72%). Physeal status was closed/closing in 32 patients (59%) and open in 22 patients (41%). On MRI, the cartilage was predicted to be disrupted in 40 patients (74%) and intact in 14 patients (26%). At the time of ankle arthroscopy, the cartilage was found to be disrupted in 38 OLTs (70%) and intact in 16 OLTs (30%). Table 1 lists variables predictive of cartilage integrity.MRI classification of cartilage integrity was 95% sensitive and 75% specific for arthroscopic integrity, with 11% misclassification. In the 16 patients less than 13 years, MRI perfectly predicted arthroscopic cartilage integrity. In patients with open physes, MRI sensitivity was 92% and specificity 100%. In patients with closing/closed physes, MRI sensitivity was 89% and specificity 50%.Receiver operator curve characteristics of a model to predict arthroscopic cartilage integrity combining MRI cartilage integrity, physeal status, and radiographic grade has an AUC of 0.955.Conclusions:Physeal status, radiographic grade, MRI grade, and cartilage integrity on MRI are independent predictors of cartilage integrity at the time of ankle arthroscopy for patients with OLTs. Overall, MRI has 95% sensitivity and 75% specificity for cartilage integrity at the time of arthroscopy, which improves to near 100% sensitivity and specificity in patients with open physes. A model combining MRI cartilage integrity, physeal status, and radiographic grade has the highest predictability of intra-operative cartilage integrity.

Quercetin suppresses apoptosis of chondrocytes induced by IL‑1β via inactivation of p38 MAPK signaling pathway

The objective of the present study was to investigate the effect of quercetin and evaluate its protective effect on articular cartilage in patients with osteoarthritis (OA), by intervening the p38 pathway. The target factors of quercetin protecting articular cartilage in patients with OA were predicted scientifically and analyzed to predict the possible pathways by using network pharmacology. A pathway predicted to be closely associated with osteoarthritis was chosen for experimental verification in in vitro cells. The optimal intervention drug concentrations were selected by the of Cell Cycle Kit-8 assay, osteoarthritis and inflammatory factors relevant to osteoarthritis, interleukin-1β and tumor necrosis factor-α, were tested by of enzyme-linked immunosorbent assay, and the expression of relevant proteins and mRNA of the p38 signaling pathway was tested by reverse transcription-quantitative PCR and western blotting, following quercetin intervention. It was found that quercetin, at the concentration of 100 umol/l, can decrease inflammatory factors relevant to OA, inhibit the expression of p38, matrix metalloprotease 13 and ADAMTS in the pathway, and promote the expression of collagen Ⅱ. Therefore, it is postulated that quercetin can lower the expression of inflammatory factors in cartilage for the prevention and treatment of OA, and the expression level of relevant factors can be changed positively by blocking the p38 MAPK signaling pathway. Thus, quercetin can promote the repair of degenerative chondrocytes and protect articular chondrocytes.

Long term usage of dexamethasone accelerating accelerates the initiation of osteoarthritis via enhancing chondrocyte apoptosis and the extracellular matrix calcification and apoptosis of chondrocytes.

Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice. Long-term administration of Dex aggravates the proteoglycan loss of articular cartilage and drastically accelerates cartilage degeneration under surgically induced OA conditions. In addition, Dex increases calcium content in calcified cartilage layer of mice and the samples from OA patients with a history of long-term Dex treatment. Moreover, long term usage of Dex results in decrease subchondral bone mass and bone density. Further studies showed that Dex leads to calcification of extracellular matrix of chondrocytes partially through activation of AKT, as well as promotes apoptosis of chondrocytes in calcified cartilage layer. Besides, Dex weakens the stress-response autophagy with the passage of time. Taken together, our data indicate that long-term application of Dex may predispose patients to OA and or even accelerate the OA disease progression development of OA patients.

T1ρ Mapping of Subtalar Articular Cartilage in Patients with Ankle Osteoarthritis

T1ρ Mapping of Subtalar Articular Cartilage in Patients with Ankle Osteoarthritis

Articular Cartilage in Patients with Knee Osteoarthritis Due to Microscope

Articular Cartilage in Patients with Knee Osteoarthritis Due to Microscope

Current knowledge on the genetic background of developmental dysplasia of the hip and the histomorphological status of the cartilage

Developmental dysplasia of the hip (DDH) represents a morphological abnormality characterized by the incongruity of femoral head and acetabulum. It ranges from mild dysplastic changes to complete dislocation. DDH has been associated with several hereditary and environmental risk factors, which could explain the incidence variability among different countries. Numerous genes may be involved in the disease etiology and progression. However, there are controversies in the literature regarding some of these genes. DDH-induced secondary osteoarthritis (OA) is characterized by changes in the macromolecule content of the cartilage and the expression of cartilage degradation markers. In addition, it exhibits a pattern of specific histological changes, with several reported differences between primary and DDH-induced secondary OA. The articular cartilage of patients with DDH shows specific radiological characteristics, including changes visible already in infancy, but also at pre-arthritic stages, early stages of OA, and in fully developed DDH-induced secondary OA. Although DDH has been extensively researched in different disease stages, the etiology of the disorder still remains uncertain. This review focuses on the current knowledge on the histomorphological status of the cartilage and the genetic background of DDH.

Regulation and function of SOX9 during cartilage development and regeneration.

Chondrogenesis is a highly coordinated event in embryo development, adult homeostasis, and repair of the vertebrate cartilage. Fate decisions and differentiation of chondrocytes accompany differential expression of genes critical for each step of chondrogenesis. SOX9 is a master transcription factor that participates in sequential events in chondrogenesis by regulating a series of downstream factors in a stage-specific manner. SOX9 either works alone or in combination with downstream SOX transcription factors, SOX5 and SOX6 as chondrogenic SOX Trio. SOX9 is reduced in the articular cartilage of patients with osteoarthritis while highly maintained during tumorigenesis of cartilage and bone. Gene therapy using viral and non-viral vectors accompanied by tissue engineering (scaffolds) is a promising tool to regenerate impaired cartilage. Delivery of SOX9 or chondrogenic SOX Trio into cells produces efficient therapeutic effects on chondrogenesis and this event is facilitated by scaffolds. Non-viral vector-guided delivery systems encapsulated or loaded in mechanically stable solid scaffolds are useful for the regeneration of articular cartilage. Here we review major milestones and most recent studies focusing on regulation and function of chondrogenic SOX Trio, during chondrogenesis and cartilage regeneration, and on the development of advanced technologies in gene delivery with tissue engineering to improve efficiency of cartilage repair process.

Clinical and morphological features of age-related, posttraumatic and metabolic phenotypes of late stage knee osteoarthritis

Purpose: To verify clinical, functional, and morphological differences among age-related, posttraumatic and metabolic osteoarthritis (OA) phenotypes in patients with advanced gonarthrosis. Methods: The study covered 120 patients with gonarthrosis (Altman R.D., 1991) of III-IV radiological stages (Kellgren and Lawrence, 1957) hospitalized for total knee replacement. Age-related (over 50 years, absence of previous joint injury and metabolic syndrome, normal body mass index), posttraumatic, metabolic, mixed phenotypes (combination of all factors) were identified and studied, taking into account influence of the most common OA risk factors and proposed classifications in scientific literature (G.Musumeci et al., 2015; A.Dell'Isola et al., 2016; G.Herrero-Beaumont et al., 2017). There were 30 people in every group, and the informed consent was obtained. All patients have undergone clinical examination with filling out WOMAC questionnaire, algofunctional Lequesne index for knee OA, Visual Analogue Scale (VAS). To assess the quality of life the questionnaire MOS SF-36 was used. In 10 patients of every group (total n=40), histopathological study of medial tibiofemoral condyle cartilage and areolar synovial membrane of knee joints was performed using histochemical methods, Mankin H.J.(1971) and Krenn V.(2002) scales. Quantitative data were processed statistically. Results: Female predominance was found in all groups, however the largest number of women was found in metabolic (n=26, 86.7%) and mixed (n=26, 86.7%) phenotypes in comparison with age-related OA (n=18, 60%; р=0,019). The average age of patients with age-related phenotype was the highest (72,5[63; 77] years), and significant differences were detected compared with posttraumatic (62,5 [59; 64] years, p=0.001), metabolic (63 [57;68] years, p = 0.010), mixed (60 [56;64] years, p=0.001) OA. Synovitis was revealed significantly more frequently in metabolic OA (n=23, 76.7%) in comparison with age-related phenotype (n=13, 43.3%; р=0.008). The pain level according to VAS corresponded to severe (7-8 points) in all patients and did not have significant differences between the groups. The highest values of WOMAC questionnaire were found in metabolic phenotype (188 [162;207]), the lowest - in posttraumatic OA (129 [100;166], р=0,001). Lequesne index was the lowest in patients with posttraumatic phenotype (15 [14;19]) and the highest in patients with age-related and metabolic OA (20 [18;21], р=0,004; 20 [19;23], р=0,003, respectively). The lowest values of quality of life were in group of patients with metabolic phenotype (Physical Health - 28 [24.3;31.9], Mental Health - 30.9 [26.9;35.9]), the highest - in posttraumatic OA (34,1 [30,5;36,1], р=0,014 and 40,4 [32,9;43,8], р=0,005, respectively). Histopathological study showed that articular cartilage of patients with age-related OA phenotype was characterized by deep erosions, denudation of subchondral bone, hypocellularity, severe decrease of proteoglycans content. In synovial membrane, lipomatosis and severe inflammatory infiltration were found. In posttraumatic OA numerous surface defects, fibrous cartilage replacement, and chondrocyte clustering were revealed in articular cartilage, and fibrosis was detected in synovial membrane. In metabolic phenotype pronounced vascularization, ossification of articular cartilage, synovial hyperplasia, microcirculation disorders and monocyte/macrophage infiltration were observed. Mixed OA was characterized by combination of variable sings. The most severe cartilage damage according to Mankin scale was shown in age-related OA (8.5 [6;10] points). Significant differences were found in comparison with metabolic phenotype (6 [4.5;6.5] points; (р=0,001). High-grade synovitis was detected in patients with age-related and metabolic OA (5 [3;8] and 4 [3;5] points by Krenn scale, respectively). Conclusions: Age-related, posttraumatic and metabolic OA phenotypes in patients with III-IV radiological stages of gonarthrosis are characterized by various clinical and morphological features. In age-related OA phenotype late clinical debut, moderate pain and dysfunction of knee joints, severe degenerative-dystrophic changes in cartilage and synovial membrane were observed. Posttraumatic OA phenotype was characterized by mild clinical and functional disorders, acceptable quality of life of patients, severe cartilage damage, activation of reparative mechanisms, synovial fibrosis. In metabolic OA phenotype female predominance, frequent clinical synovitis, pronounced clinical and functional manifestations, low quality of patients life, cartilage vascularization and ossification, severe synovial microcirculation disorders were found. Mixed OA phenotype was characterized by variable clinical and morphological picture.

OSTEOCHONDRAL LESIONS OF THE TALUS: FACTORS PREDICTIVE OF CARTILAGE INTEGRITY

Background:The integrity of articular cartilage in patients with osteochondral lesions of the talus (OLTs) guides treatment. The ability to predict cartilage integrity in OLTs, as previously published for OCD of the knee1, would be beneficial. The purpose of this study is to evaluate the association of radiographic and MRI findings and articular cartilage integrity at the time of ankle arthroscopy for OLTs.Methods:A single-institution retrospective review identified patients 19 years of age and younger with operative treatment of OLTs from 2010 – 2017. Demographics and intra-operative findings at the time of ankle arthroscopy were identified by chart review. Radiographs were assessed for physeal status, OLT location, and Berndt and Hardy grade. MRIs were reviewed for OLT size and location, modified Kramer grade, and cartilage status.Results:53 patients with 54 OLTs and a mean age of 13.6 years (range 7 – 19 years) were included. OLTs were located in the posteromedial talus in 39 patients (72%). Physeal status was closed/closing in 32 patients (59%) and open in 22 patients (41%). On MRI, the cartilage was predicted to be disrupted in 40 patients (74%) and intact in 14 patients (26%). At the time of ankle arthroscopy, the cartilage was found to be disrupted in 38 OLTs (70%) and intact in 16 OLTs (30%). Table 1 lists variables predictive of cartilage integrity.Table 1.Summary of Cohort: Overall and by Cartilage Integrity Determined by ArthroscopyVariableLevelNOverallDisruptedIntactP-ValueN=54N=38N=16Physeal Statusclosed5427 (50%)22 (57.89%)5 (31.25%) 0.018 closing5 (9.26%)5 (13.16%)0 (0.00%)open22 (40.74%)11 (28.95%)11 (68.75%)Radiographic Grade15414 (25.93%)4 (10.53%)10 (62.5%) <.001 2 16 (29.63%)11 (28.95%)5 (31.25%) 3 20 (37.04%)19 (50%)1 (6.25%) 4 4 (7.41%)4 (10.53%)0 (0.00%) MRI Grade15414 (25.93%)2 (5.26%)12 (75%) <.001 2 25 (46.3%)22 (57.89%)3 (18.75%) 3 14 (25.93%)13 (34.21%)1 (6.25%) 4 1 (1.85%)1 (2.63%)0 (0.00%) Cartilage on MRIDisrupted5440 (74.07%)36 (94.74%)4 (25%) <.001 Intact 14 (25.93%)2 (5.26%)12 (75%) MRI classification of cartilage integrity was 95% sensitive and 75% specific for arthroscopic integrity, with 11% misclassification. In the 16 patients less than 13 years, MRI perfectly predicted arthroscopic cartilage integrity. In patients with open physes, MRI sensitivity was 92% and specificity 100%. In patients with closing/closed physes, MRI sensitivity was 89% and specificity 50%.Receiver operator curve characteristics of a model to predict arthroscopic cartilage integrity combining MRI cartilage integrity, physeal status, and radiographic grade has an AUC of 0.955.Conclusions:Physeal status, radiographic grade, MRI grade, and cartilage integrity on MRI are independent predictors of cartilage integrity at the time of ankle arthroscopy for patients with OLTs. Overall, MRI has 95% sensitivity and 75% specificity for cartilage integrity at the time of arthroscopy, which improves to near 100% sensitivity and specificity in patients with open physes. A model combining MRI cartilage integrity, physeal status, and radiographic grade has the highest predictability of intra-operative cartilage integrity.SIegaSll E, Faust JR, Herzog MM, Marshall KW, Willimon SC, Busch MT. Age predicts disruption of the articular surface of femoral condyles in knee OCD: can we reduce usage of arthroscopy and MRI? J Pediatr Orthop 2018;38:176-180.