Femoral Articular Cartilage Research Articles

Effectively Measuring Exercise-Related Variations in T1ρ and T2 Relaxation Times of Healthy Articular Cartilage.

Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. Prospective observational study. Phantom and 19 healthy participants. 3T; 3D fat-saturated spoiled gradient recalled-echo; T1ρ - and T2 -prepared pseudosteady-state 3D fast spin echo. The intrasessional repeatability of T1ρ and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1ρ and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. Without knee repositioning, both surface-averaged T1ρ and T2 were very repeatable on all cartilage surfaces, with RMS-CV <1.1%. Repositioning of the knee had the greatest effect on T1ρ of patellar cartilage with the surface-averaged RMS-CV = 4.8%. While T1ρ showed the greatest response to exercise at the patellofemoral cartilage region, the largest changes in T2 were determined in the lateral femorotibial region. Following thresholding, significant (>SDD) average exercise-induced in T1ρ and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. Joint-loading with a stepping activity resulted in T1ρ and T2 changes above background measurement error. 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.

Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig

Iron is emerging as a key player in aging-associated diseases due to its propensity for driving free radical formation. Studies examining the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. Our objective was to establish a direct relationship between excess iron and OA by administering iron dextran to a guinea pig strain with decreased propensity for developing this disease. Twenty, 12-week-old Strain 13 guinea pigs received either iron dextran or dextran control intraperitoneally once weekly for 4 weeks; termination occurred at 16 weeks of age. Iron levels were determined systemically (serum and liver) and within diarthrodial joints [femoral head articular cartilage and infrapatellar fat pads (IFPs) of knee joints]. One knee was collected to score structural changes associated with OA via microcomputed tomography (microCT) and histology using published grading schemes. Articular cartilage and IFPs were harvested from contralateral knees for gene expression analyses. Iron overload was confirmed systemically via increased serum iron and liver iron concentration. Articular cartilage and IFPs in the iron dextran group also had higher levels of iron. Excess iron worsened knee OA using both microCT and histologic scoring systems. Gene analyses revealed that exogenous iron altered the expression of iron trafficking proteins, select cytokines, and structural components of cartilage. These results demonstrate that systemic iron overload caused cellular iron accumulation in the knee joint. This excess iron is associated with increased expression of local inflammatory mediators and early onset and progression of knee joint OA in Strain 13 animals.

Are Chondrocytes Overlying Cam Morphology Suitable for Therapeutic Use?

Objectives:Cam-type femoroacetabular impingement (FAI) results in extra bone and cartilage on the anterolateral femoral head-neck junction, causing abnormal contact between the femur and the acetabulum. We investigated whether chondrocytes isolated from cam lesions in FAI patients are metabolically similar to normal chondrocytes and therefore a potential option for therapeutic use via autologous implantation.Methods:Cam cartilage was obtained intraoperatively from 7 human patients with cam lesions (Alpha angle > 60 degrees) (4 arthroscopy, 2 arthroplasty, and 1 periacetabular osteotomy). Healthy femoral and acetabular articular cartilage was obtained from 8 Yucatan minipig hips for comparison. Chondrocytes were extracted from the cartilage then cultured at a high density for up to 1 week. Mitochondrial stress testing procedures (with 2 mM oligomycin, 2.5 mM carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP), 2 mM rotenone, 5 mM antimycin A) for determination of the chondrocytes basal and maximal respiration were performed.Results:No significant differences in basal (p = 0.73) or maximum (p = 0.40) respiration were found when comparing chondrocytes from cam lesions to normal porcine articular chondrocytes. There was a significant difference in maximum respiration when comparing chondrocytes from cam lesions in patients who underwent a total hip arthroplasty to chondrocytes from other cam lesions (p = 0.007).Conclusion:Basal and maximum respiration in chondrocytes from cartilage overlying cam lesions suggests a similar level of respiration to healthy articular chondrocytes. Given the importance of mitochondria to cartilage homeostasis, this study supports that chondrocytes overlying non-arthritic femoral cam lesions may be a novel source of healthy chondrocytes.

Histopathological Findings of Failed Free Vascularized Fibular Grafting for Osteonecrosis of the Femoral Head after Long-Term Follow-Up.

Purpose The aim of this study was to report the histopathology of failed free vascularized fibular grafting (FVFG) for osteonecrosis of the femoral head (ONFH) after a mean follow-up of 11.5 years (ranged from 10.6 to 14.2 years). Methods Six hips of 5 patients with a history of steroid use, aged 34–67 years, were in stage II of ONFH as classified by the Ficat and Arlet classification at the time of FVFG treatment. Grafting failure led to osteoarthritis of the hip joint during a mean of 11.5 years of follow-up. Femoral head specimens were first evaluated macroscopically. Bone specimens were sectioned into long strips, divided into necrotic, transitional, and healthy zones, and then prepared for nondecalcified and decalcified histopathological examination using hematoxylin and eosin (HE) staining, Goldner's trichrome staining, and immunofluorescence (IF) staining. Results Femoral head articular cartilage surfaces appeared thin, opaque, and partially cartilaginous missing, with gradual collapse detected in weight-bearing areas. The interface with the fibular graft showed well union, with no obvious gaps between graft and host bone, as observed macroscopically. The necrotic area was filled with fibular graft, cancellous bone, and cartilaginous or soft tissue invasion. Histopathology results revealed well integration between fibular graft and host bone, with thickened trabecular bone. Gaps occurred in transitional and healthy zones. In the necrotic zone, cartilaginous or soft tissue invasion occurred, while thin or missing articular cartilage exposed subchondral bone to hip joint surfaces. By IF counterstaining with CD-31 and α-SMA, blood vessel transplanted during fibular grafting could be clearly observed along the graft from healthy to necrotic zones. In the necrotic zone, blood vessels presented obviously and spread into the surrounding area of the graft tip. Conclusion After FVFG procedure with a mean follow-up of 11.5 years, fibular grafts retained their integrity as viable, vascularized, cortical bone that fused well with host bone and formed thickened trabecular bone surrounding the surface of the graft. However, the revascularization of FVFG's blood vessels spreading from the tip of the fibular graft into subchondral area of necrotic lesion did not improve significantly in these failure cases. The local necrotic lesion failed to be repaired as healthy trabecular bone to buttress articular surface and was occupied by soft tissues.

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.

Depth-dependent changes in cartilage T2 under compressive strain: a 7T MRI study on human knee cartilage

To assess the potential of using ΔT2 as an indirect index of cartilage strain by quantifying the relationship between local in situ compressive strain and ΔT2 through the full depth of human tibial and femoral articular cartilage. Osteochondral samples (n=4) of human tibial and femoral cartilage were harvested from cadavers and imaged in a Bruker 7T research MRI scanner under increasing displacement-controlled compressive strains. T2 was calculated for 3D double echo steady state (DESS) image volumes at each strain level. A decaying exponential model estimated local, depth-dependent strains. Strained image volumes were non-linearly warped back to their unloaded configurations and ΔT2 was calculated by image subtraction. Linear modeling assessed local relationships between strain and ΔT2. Bulk average tibial T2 was 13.2ms for unstrained cartilage and ranged from 13.0 to 13.1ms under strain; femoral T2 was 14.0ms for unstrained cartilage and ranged from 13.5 to 14.8ms under strain. Local ΔT2 in strained cartilage varied with depth. Linear modeling revealed significant correlations between in situ strain and ΔT2 for both tibial and femoral cartilage; correlation coefficients were higher for tibial cartilage. Changes in bulk average T2 are unsuitable as a quantitative surrogate measure of cartilage strain because bulk averaging masks important local variations. High-resolution measures of local ΔT2 have potential value as a surrogate for strain; however, their value is limited until we fully understand the influence of factors like age, joint surface and degeneration on the strain vs T2 relationship.

Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population.

Chemical exchange saturation transfer of glycosaminoglycans, gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 T and higher. However, its utility at 3 T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3 T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison with T2 and T1ρ measures. We hypothesize that gagCEST asymmetry at 3 T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including 10 healthy subjects and 32 subjects with medial OA, were included in the study. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects, and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3 T to assess the repeatability of the volumetric gagCEST sequence at 3 T. For healthy and OA subjects, gagCEST asymmetry and T2 and T1ρ relaxation times were calculated for the femoral articular cartilage to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single-slice acquisitions (p = 0.015). The average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T2 and T1ρ relaxation times were elevated in OA subjects (p < 0.001 for both) compared with healthy controls and both were moderately correlated with total KOOS scores (rho = -0.181 and rho = -0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 min and high gagCEST asymmetry at 3 T, did not vary significantly between healthy subjects and those with mild-moderate OA. This further supports a limited utility for gagCEST imaging at 3 T for assessment of early changes in cartilage composition in OA.

Can Ellipsoid Sign be One of the Earliest Findings of the Medial Femoral Condyle Chondromalacia of Knee Antero Posterior X-Ray?

Aim of the study was to investigate whether ellipsoid sign (ES) in the region corresponding to the cartilaginous facet of the medial femoral condyle (MFC) indicates early cartilage lesion. The finding has not been defined in the literature yet. The study was performed retrospectively with 50 patients who underwent articular cartilage examination and arthroscopy between 2015 and 2018. Patients were divided into two according to the presence or absence of ES. There were 24 patients in case group (Group A) and 26 patients in controls (Group B). Weight-bearing cartilage areas of MFC in the region where ES was found in both groups were classified according to arthroscopic Outerbridge classification (OC) and compared statistically with each other. There was no significant difference in terms of age, gender and alignment between Group A and Group B (p > 0.05). All OC grades were higher in Group A (p < 0.001). Positive correlation between ES and MFC chondromalacia grade was detected (r: 0.671, t: 6.266, p < 0.05). ES, which refers to the difference in bone density in MFC seen in antero-posterior (AP) X-Ray, is a result of changes in subchondral bone due to chronic cartilage loss. ES detected on AP X-Ray may help in early diagnosis of medial femoral articular cartilage chondromalacia, even at grade 0 or 1. We recommend searching for ES, as the earliest symptom of chondromalacia, which occurs even before MRI lesions. Future studies may reveal additional information about ES.

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.

Physeal-sparing posteromedial portal approach reduced distance between guide pin and neurovascular structures

To compare a femoral physeal sparing anterior cruciate ligament (ACL) reconstruction technique utilizing a posteromedial portal to traditional transphyseal techniques with regards to anatomic tunnel positioning and proximity to important neurovascular structures. Eight cadaveric knees were obtained for the study. Femoral tunnel guide pins were placed utilizing four different techniques: accessory anterior medial portal, posteromedial portal, trans-tibial, and figure-4 methods. The knees were then dissected and the following measurements taken: distance of each pin to the saphenous and peroneal nerve, popliteus tendon, neurovascular bundle, femoral ACL footprint and articular cartilage, and the angle of the guide pin entering the lateral femoral condyle. Fluoroscopic imaging was taken to determine the disruption of the physeal scar. Posteromedial portal guide pin was significantly closer to the neurovascular bundle, popliteal tendon and saphenous nerve when compared to the other 3 techniques, but was further from the peroneal nerve. It also had the smallest distance from the anatomic footprint of the ACL, and the largest angle to the lateral femoral condyle. The posteromedial portal guide pin had similar distance from the articular cartilage as the accessory anterior medial portal and figure-4 guide pin, with the trans-tibial guide pin being the farthest. The posteromedial portal guide pin failed to disrupt the physeal scar in all specimens, while the other three techniques consistently violated the physeal scar. The posteromedial portal technique offers an appropriate method for anatomic ACL reconstruction while protecting the distal femoral physis from injury. Care needs to be taken with this technique as it comes in closer proximity to some of the important neurovascular structures. This study indicates that posteromedial portal technique is a less technically challenging approach for physeal-sparing ACL repair with special attention required for the protection of neurovascular bundle from potential injury.

Characterization of the interleukin-17 effect on articular cartilage in a translational model: an explorative study

BackgroundOsteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. The aim of this study was to characterize an IL-17-mediated articular cartilage degradation ex-vivo model and to investigate IL-17 effect on cartilage extracellular matrix protein turnover.MethodsFull-depth bovine femoral condyle articular cartilage explants were cultured in serum-free medium for three weeks in the absence, or presence of cytokines: IL-17A (100 ng/ml or 25 ng/ml), or 10 ng OSM combined with 20 ng/ml TNFα (O + T). RNA isolation and PCR analysis were performed on tissue lysates to confirm IL-17 receptor expression. GAG and ECM-turnover biomarker release into conditioned media was assessed with dimethyl methylene blue and ELISA assays, respectively. Gelatin zymography was used for matrix metalloproteinase (MMP) 2 and MMP9 activity assessment in conditioned media, and shotgun LC-MS/MS for identification and label-free quantification of proteins and protein fragments in conditioned media. Western blotting was used to validate MS results.ResultsIL-17RA mRNA was expressed in bovine full-depth articular cartilage and the treatment with IL-17A did not interfere with metabolic activity of the model. IL-17A induced cartilage breakdown; conditioned media GAG levels were 3.6-fold-elevated compared to untreated. IL-17A [100 ng/ml] induced ADAMTS-mediated aggrecan degradation fragment release (14-fold increase compared to untreated) and MMP-mediated type II collagen fragment release (6-fold-change compared to untreated). MS data analysis revealed 16 differentially expressed proteins in IL-17A conditioned media compared to untreated, and CHI3L1 upregulation in conditioned media in response to IL-17 was confirmed by Western blotting.ConclusionsWe showed that IL-17A has cartilage modulating potential. It induces collagen and aggrecan degradation indicating an upregulation of MMPs. This was confirmed by zymography and mass spectrometry data. We also showed that the expression of other cytokines is induced by IL-17A, which provide further insight to the pathways that are active in response to IL-17A. This exploratory study confirms that IL-17A may play a role in cartilage pathology and that the applied model may be a good tool to further investigate it.

Ultrasound-based cartilage outcomes differentiate healthy and medial femoral cartilage damage after anterior cruciate ligament injury: A preliminary investigation

Purpose: Ultrasound imaging is a clinically feasible tool to assess femoral articular cartilage following acute knee injuries. Previous studies have validated an ultrasound assessment of femoral cartilage thickness. However, traditional ultrasound cartilage thickness assessments rely on a single straight-line distance and do not determine the mean thickness throughout a cartilage region. Further, it is unknown whether ultrasound echo-intensity (i.e., magnitude and variation of the pixel signal intensity) is related to cartilage damage following anterior cruciate ligament injury.

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.

Understanding the undulating pattern of the distal femoral growth plate: Implications for surgical procedures involving the pediatric knee: A descriptive MRI study

IntroductionOperative procedures near the distal femoral physis can result in iatrogenic damage if one is not familiar with the complex anatomy of the growth plate. The purpose of this study was to use physeal-specific MRI sequences to delineate the anatomic dimensions of the distal femoral physis. Materials and methodsSixty patients underwent physeal-specific spoiled gradient 3-D fat saturated (SPGR) MRI analysis of a single knee. Three age groups (eight to 10, 11–13, and 14–16 years) comprised of equal numbers (n = 20) of boys and girls were evaluated. Using the SPGR coronal sequence, the distance of the physis to the femoral articular cartilage was recorded at the medial, mid-medial, notch, mid-lateral and lateral margins of the knee. Coronal measurements were recorded at four locations along the sagittal sequence, as the anteroposterior dimension of the knee was divided into equal quartiles. ResultsWhile little variation in shape was observed in the anterior quartile, the remaining quartiles demonstrated significant variability that increased moving posteriorly (p < .001), therefore reflecting a more concave shape in the posterior aspect of the femur. These observations were statistically significant for age at the posterior two quartiles. ConclusionThese MRI data suggest that while the physis is linear in the anterior part of the femur, it possesses a more concave shape in the posterior aspect of the medial and lateral condyles. Findings were preserved across gender and age. Ultimately, these data can aid in preoperative planning and should be considered when performing operative procedures in the skeletally immature knee.

Enoxolone suppresses apoptosis in chondrocytes and progression of osteoarthritis via modulating the ERK1/2 signaling pathway.

Osteoarthritis (OA) is an inflammatory disorder of synovial joints which is mainly treated with therapeutic agents showing side effects associated with the gastrointestinal (GI) and metabolic system. Consequently, there is urgent need for a potent, safe and novel agent for treating OA and related disorders. Enoxolone is a pentacyclic triterpenoid obtained from the herb liquorice. Based on earlier findings, we postulated that enoxolone may produce chondroprotective activity by exerting anti-inflammatory, anti-catabolic and oxidative stress-decreasing effects. The chondrocytes were extracted from the femoral head articular cartilage of healthy rats. Immunofluorescence staining was done for identification of chondrocytes. Cell viability and proliferation studies were done using Cell Counting Kit-8. Apoptotic cells were identified by TUNEL assay and flow cytometry analysis. Autophagy was assessed by monodansylcadaverine assay. Western blot analysis was done for expression of proteins. In the present study we investigated the protective effect of enoxolone on interleukin 1β (IL-1β) treated Iry chondrocytes in vitro. Treatment with IL-1β resulted in a significant reduction in cell viability of cells in increasing dose and time. Treatment with enoxolone along with IL-1β caused a significant decrease in growth inhibition. Also, enoxolone inhibited the IL-1β mediated apoptosis and activation of caspase-3 in cells. We also observed that enoxolone elevated the levels of p-ERK1/2, light chain 3 (LC3)-II and Beclin-1 (autophagy markers) in chondrocytes. The expression of (LC3)-II and Beclin-1 was decreased when the cells were treated with U0126 (ERK1/2 inhibitor). Our findings demonstrate that enoxolone could suppress inflammatory signaling and apoptosis via the ERK1/2 pathway in chondrocytes.

Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model

Background: Lubricin, a mucinous glycoprotein, plays a chondroprotective role as a constituent of synovial fluid. Structural analogs have been synthesized to mimic the structure and function of native lubricin in an effort to recapitulate this effect with the goal of delaying progression of osteoarthritis (OA). Purpose: To investigate the efficacy of intra-articular injections of lubricin mimetics in slowing or preventing the progression of posttraumatic OA by using a rat anterior cruciate ligament transection model. Study Design: Controlled laboratory design. Methods: Four lubricin mimetics were investigated, differing from one another in their binding orientations and steric interactions. Eighty skeletally mature Sprague-Dawley rats underwent bilateral anterior cruciate ligament transections and were randomly allocated to receive intra-articular injections (50 µL/injection) of 1 of the 4 mimetics in the right knee and equal volumes of saline injection in the contralateral knee (control). All rats were euthanized 8 weeks postoperatively and assessed via biomechanical analysis, which evaluated comparative friction coefficients across the 4 groups, and histological evaluation of articular cartilage, osteophytes, and synovitis. The Osteoarthritis Research Society International (OARSI) histopathological assessment system was used to evaluate the degree of articular cartilage degeneration and osteophytes, while synovitis was assessed through a semiquantitative scoring system. Binding efficacy of the 4 mimetics was assessed in vitro and in vivo through the immunohistochemical localization of polyethylene glycol. Articular cartilage degeneration and synovitis scoring data analyses were performed with generalized estimating equation modeling. Results: Injection of the group 3 mimetic (random 24 + 400 + 30) directly correlated with improved OARSI scores for femoral articular cartilage degeneration when compared with saline-injected contralateral control knees (P = .0410). No lubricin mimetic group demonstrated statistically significant differences in OARSI scores for tibial articular cartilage degeneration. Injection of the group 4 mimetic (AB 24 + 400 + 30) led to a statistically significant difference in osteophyte OARSI score (P = .0019). None of the 4 lubricin mimetics injections incited an additive synovial inflammatory response. Immunohistochemical staining substantiated the binding capacity of all 4 mimetics, while in vivo experimentation revealed that the group 1 and 3 mimetics were still retained within the joint 4 weeks after injection. There were no differences in friction coefficients between any pair of groups and no significant trends based on lubricin mimetic structure. Conclusion: We demonstrated that the tribosupplementation of a traumatically injured knee with a specific lubricin structural analog may attenuate the natural progression of OA. Clinical Relevance: The current lack of efficacious clinical options to counter the onset and subsequent development of OA suggests that further investigation into the synthesis and behavior of lubricin analogs could yield novel translational applications.

Knee Arthroscopy: The “Crevice Sign,” a New Pathognomonic Sign for Unstable Posterior Medial Meniscal Tear in Anterior Cruciate Ligament–Deficient Knees

There has been increased emphasis on medial meniscus repair in the anterior cruciate ligament–reconstructed knee, as this improves stability. We describe an arthroscopic sign of an unstable medial meniscal tear that is diagnostic. The “crevice sign” is a longitudinal fissure located on the distal medial femoral condyle. In the anterior cruciate ligament–deficient knee, there is increased strain on the medial meniscus. A posterior longitudinal medial meniscal tear can occur at the time of the index injury or with subsequent instability events. During this injury, the knee pivots and the anterior edge of the unstable medial meniscus digs into the articular cartilage of the medial femoral condyle, resulting in a longitudinal split of the distal femoral condyle articular cartilage. If this sign is observed during arthroscopy, it is recommended that surgeons thoroughly probe the medial meniscus to ensure no pathology is missed.

Arthroscopic treatment of chondral lesions in varus knee in adults combined with corrective high tibial osteotomy

Objectives To document whether cartilage regeneration occurs in the degenerated medial compartment of arthritic knees in patients with varus malalignment after medial opening wedge high tibial osteotomy (MOWHTO) with concomitant cartilage procedures and to assess which predictive factors influence the clinical outcome. Patients and methods A total of 28 patients underwent MOWHTO between December 2016 and December 2018 in Al-Zahraa University Hospital for varus malalignment and medial osteoarthritis. Preoperative and postoperative assessments were done using American Knee Society’s Knee and Functional Scoring System. All patients were evaluated by arthroscopy before and ∼12 months after HTO. The International Cartilage Repair Society grading system was used for arthroscopic grading. Results At initial arthroscopy, two (7.1%) knees had grade II medial femoral condyle articular cartilage finding, seven (25%) knees had grade III findings, and 19 (67.9%) knees had grade IV findings. Only 20 cases had second-look arthroscopy, no regenerative change was found in 40% of knees, white scattering fibrocartilage was found in 55% of knees, and deterioration of the cartilage was observed in one (5%) case. Conclusion The degenerated cartilage could be partially or entirely covered by newly regenerated cartilage at 1 years after adequate correction of varus deformity by MOWHTO.

The Role of High Resolution Ultrasound in the Assessment of Knee Osteoarthritis

AbstractBackground: Osteoarthritis (OA) is a common musculoskeletaldisease with high prevalence worldwide. Knee OAis primary diagnosed using conventional radiography, however,changes of articular cartilage or menisci cannot be directlyassessed using conventional radiology. Ultrasound (US) canbe used to assess soft tissue degeneration directly.Aim of Study: The aim of this study is to evaluate theefficacy of High Resolution Ultrasound (HRUS) in the assessmentof structural abnormalities found in knee osteoarthritis.Patients and Methods: The study was conducted upon 20patients with knee OA (12F, 8M; mean age 53 years), eachsubject was evaluated for the presence of medial and lateralfemoral cartilage thinning, medial and lateral femoral andtibial osteophytes, medial and lateral meniscal degeneration,joint effusion and Baker's cyst using ultrasound and MRI,considering MRI as a reference standard.Results: The overall sensitivity of the ultrasound in thedetection of knee OA parameters was good (89.3%), theoverall accuracy was excellent (90%), the overall specificitywas excellent (93.1%). The Positive Predictive Value (PPV)and the Negative Predictive Value (NPV) were 98.3 and 65.9respectively. The p-value was highly significant (<0.01) whencomparing assessment of knee osteoarthritis parameters betweenultrasound and MRI.Conclusion: Ultrasound assessment of the knee joint isan accurate imaging method for detection of knee osteoarthritisparameters including medial and lateral femoral articularcartilage thinning, medial and lateral osteophytes, medial andlateral meniscal degeneration, joint effusion and Baker's cyst.Thus, Knee ultrasound can be used as a complementaryimaging technique to radiography, especially when MRI isnot available, to assess tissue-specific structural OA degenerationnot detected by conventional radiographs.

HOTAIR‐induced apoptosis is mediated by sponging miR‐130a‐3p to repress chondrocyte autophagy in knee osteoarthritis

Knee osteoarthritis (KOA) is a multifactorial disease characterized by the loss of articular cartilage. Hox transcript antisense intergenic RNA (HOTAIR) long non-coding RNA (lncRNA) is highly expressed in some cases of OA; however, its role in chondrocyte apoptosis in KOA and the mechanism by which HOTAIR mediates apoptosis in chondrocytes are not completely understood. Here, we evaluated the effects of HOTAIR on chondrocyte apoptosis in KOA. Our results showed that HOTAIR expression was significantly upregulated in cartilage tissues located at the femoral condyles or tibial plateaus of OA resection regions when compared with control regions in patients with normal non-weight-bearing area femoral condyle articular cartilage. Overexpression of HOTAIR caused a sharp increase in apoptosis rates and a reduction in the viability of chondrocytes. These effects were accompanied by the upregulation of Bax expression and the proteolytic cleavage of caspase 3 expression and downregulation of survivin and Bcl-2 expression. The silencing of HOTAIR produced the opposite effects. Moreover, the cartilaginous expression of miR-130a-3p was notably reduced in the OA resection regions of KOA patients. Luciferase assays showed that HOTAIR-adsorbed and reduced the levels of miR-130a-3p in chondrocytes. Further, inhibition of miR-130a-3p remarkably promoted the apoptosis of chondrocytes and repressed cell growth, while the silencing of HOTAIR could rescue the apoptosis mediated by miR-130a-3p inhibition. Chondrocyte autophagy was suppressed in a HOTAIR-dependent, miR-130a-3p inhibitor-mediated manner. Overall, our data revealed that aberrantly high expression of HOTAIR resulted in massive apoptosis events caused by the sponging of miR-130a-3p to suppress autophagy in chondrocytes, which, in turn, might trigger KOA. Therefore, inhibition of HOTAIR-mediated apoptosis might be a potential mechanism that can be targeted by gene therapy of KOA.