Cartilage Health Research Articles

Effects of Running in Minimal and Conventional Footwear on Medial Tibiofemoral Cartilage Failure Probability in Habitual and Non-Habitual Users.

This study examined the effects of minimal and conventional running footwear on medial tibiofemoral cartilage mechanics and longitudinal failure probability. The current investigation examined twenty males who habitually ran in minimal footwear and 20 males who habitually ran in conventional footwear. Kinematic data during overground running were collected using a motion-capture system and ground reaction forces using a force plate. Medial tibiofemoral loading was examined using musculoskeletal simulation and cartilage failure probability via probabilistic modelling. In habitual minimal footwear users, peak medial tibiofemoral cartilage force, stress and strain were significantly greater in conventional (force = 7.43 BW, stress = 5.12 MPa and strain = 0.30), compared to minimal footwear (force = 7.11 BW, stress 4.65 MPa and strain = 0.28), though no significant differences in these parameters were evident in non-habitual minimal footwear users (conventional: force = 7.50 BW, stress = 5.05 MPa and strain = 0.30; minimal: force = 7.40 BW, stress = 4.77 MPa and strain = 0.29). However, in both habitual and non-habitual minimal footwear users, the probability of medial tibiofemoral cartilage failure was significantly greater in conventional (habitual = 47.19% and non-habitual = 50.00%) compared to minimal footwear (habitual = 33.18% and non-habitual = 32.81%) users. The observations from this investigation show that compared to minimal footwear, conventional footwear appears to have a negative influence on medial tibiofemoral cartilage health.

Empirical joint contact mechanics: A comprehensive review.

Empirical joint contact mechanics measurement (EJCM; e.g. contact area or force, surface velocities) enables critical investigations of the relationship between changing joint mechanics and the impact on surface-to-surface interactions. In orthopedic biomechanics, understanding the changes to cartilage contact mechanics following joint pathology or aging is critical due to its suggested role in the increased risk of osteoarthritis (OA), which might be due to changed kinematics and kinetics that alter the contact patterns within a joint. This article reviews and discusses EJCM approaches that have been applied to articulating joints such that readers across different disciplines will be informed of the various measurement and analysis techniques used in this field. The approaches reviewed include classical measurement approaches (radiographic and sectioning, dye staining, casting, surface proximity, and pressure measurement), stereophotogrammetry/motion analysis, computed tomography (CT), magnetic resonance imaging (MRI), and high-speed videoradiography. Perspectives on approaches to advance this field of EJCM are provided, including the value of considering relative velocity in joints, tractional stress, quantification of joint contact area shape, consideration of normalization techniques, net response (superposition) of multiple input variables, and establishing linkages to regional cartilage health status. EJCM measures continue to provide insights to advance our understanding of cartilage health and degeneration and provide avenues to assess the efficacy and guide future directions of developing interventions (e.g. surgical, biological, rehabilitative) to optimize joint's health and function long term.

Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis

BackgroundIron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive. PurposeThis study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation. MethodsIron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined. ResultsMicro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload. ConclusionIron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.

Techniques for Visualization and Quantification of Primary Cilia in Chondrocytes.

Primary cilia regulate and coordinate a variety of cell signaling pathways important in chondrocyte physiology and cartilage development, health, and disease. Despite this, the chondrocyte primary cilium and its associated role in cartilage biology remains poorly understood. Key to elucidating primary cilia structure and function in chondrocytes is the ability to visualize this unique structure. Here we describe materials and methods for immunofluorescence labeling, microscopy, and measurement of chondrocyte primary cilia.

Hypoxia and Wnt signaling inversely regulate expression of chondroprotective molecule ANP32A in articular cartilage

ANP32A is a key protector of cartilage health, via preventing oxidative stress and Wnt hyper-activation. We aimed to unravel how ANP32A is regulated in cartilage. A bioinformatics pipeline was applied to identify regulators of ANP32A. Pathways of interest were targeted to study their impact on ANP32A in in vitro cultures of the human chondrocyte C28/I2 cell-line and primary human articular chondrocytes (hACs) from up to five different donors, using Wnt-activator CHIR99021, hypoxia-mimetic IOX2 and a hypoxia chamber. ANP32A was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, the effect of hypoxia was examined by immunohistochemistry in mice injected intra-articularly with IOX2 after destabilization of the medial meniscus. Effects of Wnt hyper-activation were investigated using Frzb-knockout mice and wild-type mice treated intra-articularly with CHIR99021. Wnt inhibition effects were assessed upon intra-articular injection of XAV939. The hypoxia and Wnt signaling pathways were identified as networks controlling ANP32A expression. In vitro and in vivo experiments demonstrated increases in ANP32A upon hypoxic conditions (1.3-fold in hypoxia in C28/I2 cells with 95% confidence interval (CI) [1.11-1.54] and 1.90-fold in hACs [95% CI: 1.56-2] and 1.67-fold in ANP32A protein levels after DMM surgery with IOX2 injections [95% CI: 1.33-2.08]). Wnt hyper-activation decreased ANP32A in chondrocytes in vitro (1.23-fold decrease [95% CI: 1.02-1.49]) and in mice (1.45-fold decrease after CHIR99021 injection [95% CI: 1.22-1.72] and 1.41-fold decrease in Frzb-knockout mice [95% CI: 1.00-1.96]). Hypoxia and Wnt modulated ataxia-telangiectasia mutated serine/threonine kinase (ATM), an ANP32A target gene, in hACs (1.89-fold increase [95% CI: 1.38-2.60] and 1.41-fold decrease [95% CI: 1.02-1.96]). Maintaining hypoxia and limiting Wnt activation sustain ANP32A and protect against osteoarthritis.

Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.

Patellofemoral contact forces and knee gait mechanics 3 months after ACL reconstruction are associated with cartilage degradation 24 months after surgery

Evaluate patellofemoral cartilage health, as assessed by quantitative magnetic resonance imaging (qMRI) T2 relaxation times, 24-months after ACL reconstruction (ACLR) and determine if they were associated with patellofemoral contact forces and knee mechanics during gait 3 months after surgery. Thirty individuals completed motion analysis during overground walking at a self-selected speed 3 months after ACLR. An EMG-driven neuromusculoskeletal model was used to determine muscle forces, which were then used in a previously described model to estimate patellofemoral contact forces. Biomechanical variables of interest included peak patellofemoral contact force, peak knee flexion angle and moment, and walking speed. These same participants underwent a sagittal bilateral T2 mapping qMRI scan 24-months after surgery. T2 relaxation times were estimated for both patellar and trochlear cartilage. Paired t-tests were used to compare T2 relaxation times between limbs while Pearson correlations and linear regressions were utilized to assess the association between the biomechanical variables of interest and T2 relaxation times. Prolonged involved limb trochlear T2 relaxation times (vsuninvolved) were present 24-months after surgery, indicating worse cartilage health. No differences were detected in patellar cartilage. Significant negative associations were present within the involved limb for all the biomechanical variables of interest 3 months after ACLR and trochlear T2 relaxation times at 24-months. No associations were found in patellar cartilage or within the uninvolved limb. Altered involved limb trochlear cartilage health is present 24-months after ACLR and may be related to patellofemoral loading and other walking gait mechanics 3 months after surgery.

Baseline knee extension may be associated with volumetric cartilage loss in the anterolateral tibia: data from the Osteoarthritis Initiative.

Animal studies suggest regional unloading of the knee due to flexion contracture (FC) results in cartilage loss in the anterior tibia. We looked for an association between the range of knee extension and articular cartilage thickness in the tibia of patients with knee OA, using quantitative MRI data from the OA Initiative. Baseline knee extension was measured using a goniometer. Cartilage thickness was measured using 3-Tesla coronal MRI images of the knee. The tibia articular cartilage was segmented into medial and lateral regions, then further divided into anterior, central and posterior subregions. We evaluated differences between participants with and without a knee FC and associations between knee extension and cartilage thickness, including percentage denudation of bones (0 mm thickness), using linear models. A total of 596 participants were included. Participants with a knee FC had a larger percentage of denuded bone in the anterolateral tibia vs participants without FC (2.2 ± 0.7% vs 0.4 ± 0.1%; P = 0.006), and knee extension was associated with anterolateral tibia denuded bone (r = 0.16, P < 0.001). After correcting for demographics, knee alignment, and OA severity, presence of FC and lost knee extension were associated with the percentage of denuded bone in the anterolateral tibia [β = 1.702 (0.634-2.770) and β = 0.261 (95% CI 0.134, 0.388), respectively]. While causation cannot be determined in this study, limitation in knee extension was statistically associated with the percentage of denuded bone in the anterolateral tibia. These novel data support that maintaining range of motion over the entire joint surface may help preserve articular cartilage health.

Walking speed does not affect net vastus lateralis fascicle length change on average during weight acceptance

Faster walking speeds increase the demand on quadriceps muscles to produce adequate force to decelerate body mass and control knee flexion. Quadriceps fascicle behavior (i.e., fascicle length changes) influences force generation, which in turn affects mechanical loading of the articular cartilage during walking and the biochemical environment of the knee joint. The fascicle behavior underlying different walking speeds remains unclear but should be characterized to better understand how the quadriceps muscles accommodate faster walking speeds, speeds that often associate with better cartilage health outcomes. Our purpose was to quantify quadriceps muscle net fascicle length change during weight acceptance across a range of walking speeds in the context of more well-documented changes in muscle activity and knee joint moments. We hypothesized that vastus lateralis (VL) fascicles in healthy young adults would produce force with more overall lengthening in early stance at faster walking speeds with concomitant increases in muscle–tendon unit (MTU) lengthening, internal peak knee extensor moment (pKEM), vertical ground reaction force (GRF), and muscle activity. Participants walked for two-minute trials at their preferred speed and at 0.75 m/s and 1.75 m/s. We found that on average, the VL accommodates the greater mechanical demands of walking at faster speeds with greater muscle activity and while resisting muscle lengthening behavior. We infer then that tendon stretch accommodates MTU lengthening in healthy young adults across a range of speeds and suggest these results motivate additional studies aimed at evaluating VL fascicle behavior individuals with known quadriceps strength deficits, inhibition, or heightened risk for developing osteoarthritis.

Force Platforms Can Accurately Predict Knee Kinetics Limb Asymmetry With Sit-to-stands During ACL Rehabilitation

Patients with ACL reconstruction presenting with lowered internal knee extensor moment during sports and mobility tasks exhibit markers of compromised articular cartilage health. Early detection and management of their knee extensor moment deficits during rehabilitation are paramount for risk reduction of future osteoarthritis. However, the technology to obtain knee moment data requires extensive training and financial resources. We seek a more affordable and less technically demanding clinical surrogate. PURPOSE: To determine if data obtained from two force platforms can accurately predict knee extensor moment asymmetry for diagnostic and training purposes early in rehabilitation. METHODS: The study is a retrospective analysis of 14 patients with unilateral ACL reconstruction who underwent motion analysis of a self-paced sit-to-stand from a 48 cm bench. All patients were engaged in rehabilitation at the time of testing. During testing, each foot was positioned on two lengthwise-aligned force platforms. Differences between limbs were tested with paired t-tests. Stepwise linear regression predicted limb symmetry in knee extensor moment with force platform variables of limb symmetry in peak aft forces (e.g. posterior), vertical forces, and differences in the fore-aft position of each leg's center of pressure. RESULTS: Patients presented with significant (p < 0.001) interlimb differences in knee extension moment (mean ± SD: involved = 0.62 ± 0.19 Nm/kg of body mass (BM); uninvolved = 1.06 ± 0.18), vertical ground reaction forces (p < 0.001, inv = 0.56 ± 0.05 BM; uninv = 0.66 ± 0.05), and aft forces (p < 0.001, inv = 0.024 ± 0.016 BM; uninv = 0.056 ± 0.021), and nearly significant for center of pressure position (p = 0.05, involved = 0.230 ± 0.04 m; uninvolved = 0.246 ± 0.026). The regression model explained a substantial portion of limb symmetry in knee extensor moment (R-squared = 0.887, p < 0.001) with all force platform variables contributing to the final model. CONCLUSIONS: The use of force platform parameters can strongly and accurately predict knee extensor moment asymmetry in patients with ACL reconstruction during rehabilitation. This prediction cluster is a promising and affordable alternative that may function as a surrogate measure of abnormal knee moment for retraining and improved clinical reasoning.

The relationship between subchondral bone cysts and cartilage health in the Tibiotalar joint: A finite element analysis

BackgroundSubchondral bone cysts are a common presentation in ankle haemarthropathy. The relationship with ankle joint health has however not previously been investigated. The aim of this study was to assess the influence of subchondral bone cysts of differing shapes, volumes and depths on joint health. MethodsChronologically sequential Magnetic Resonance imaging scans of four hemophilic ankles with subchondral bone cysts present (N = 18) were used to build patient specific finite element models under two cystic conditions to assess their influence on cartilage contact pressures. Variables such as location, volume and depth were considered individually, to investigate whether certain cystic conditions may be more detrimental to cartilage health. FindingsSignificant quantifiable contact redistribution was seen in the presence of subchondral bone cysts and this redistribution reflected the shape and size of the cysts, however, with the presence of cysts in both bones in 10 of the 18 cases a direct relationship to volume could not be correlated. InterpretationThis work demonstrated a redistribution of contact pressures in the presence of subchondral bone cysts. This alteration to loading history could be linked to cartilage degeneration due to the biological response to abnormal loading.

A Key Metabolic Regulator of Bone and Cartilage Health.

Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine–bone interactions and covers recently discovered aspects of taurine’s effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine–cartilage relationship.

Association of patella alignment with cartilage relaxation times and self-reported symptoms in individuals with patellofemoral degeneration.

To determine the cross-sectional and longitudinal associations of patella alignment with cartilage relaxation and patients' self-reported symptoms. Thirty participants with isolated patellofemoral joint (PFJ) degeneration (six males, 53.7 ± 9.3 years) and 24 controls (12 males, 47.6 ± 10.7 years) were included. Magnetic resonance assessment was performed to provide grading of structural abnormalities, cartilage relaxation times, and patella alignment. Self-reported symptoms were assessed using the self-administrated knee injury and osteoarthritis outcome score (KOOS). All participants were examined at baseline and 3 years. Statistical parametric mapping and Pearson partial correlation were used to evaluate the associations between patella alignment with cartilage relaxation times and self-reported symptoms, respectively. The analyses were performed between baseline (cross-sectional) as well as the baseline against 3 years (longitudinal). Results indicated that patella height and patella flexion were associated with T1ρ and T2 relaxation times at baseline (percentages of voxels showing significant correlation [PSV] = 10.1%-24.8%; mean correlations [R] = 0.34-0.36; mean p = 0.015-0.026). Furthermore, greater patella lateral alignment, lateral tilt, and lateral spin were associated with longer T2 times at 3 years (PSV = 11.0%-14.4%, R = 0.39-0.44, p = 0.017-0.028). Last, a higher patella was associated with a lower KOOS at baseline and at 3 years (R = -0.33 to -0.35). The study suggests that patella malalignment is a risk factor for worsening cartilage health, informing clinicians of a better rehabilitation program that targets PFJ degeneration.

Automated Detection of Knee Cartilage Region in X-ray Image

The prevalence of a symptomatic knee or osteoarthritis (OA) is approximately 9.6% in men and 18.0% in women over 60 years of age according to the OARSI 2016 report. Using early on-stage clinical qualitative assessments through means of X-ray scans, the cartilage health and degradation of an individual can be monitored through cartilage shape and surface over time. In this paper, we implement the application of transfer learning models such as InceptionV3, Xception and DenseNet201 for feature extraction of a rebalanced 1,000 knee X-ray images taken from Osteoarthritis Initiative (OAI) dataset with 5 classes graded 0–4 according to Kellgren-Lawrence grading split into a 70/15/15 training/validation/testing split. The features extracted are subsequently fed into machine learning classifiers, namely support vector machine (SVM). An average multiclass accuracy of 71.33% was achieved for hyperparameter fine-tuned DenseNet201-SVM model.

Effects of Male and Female Sex on the Development of Posttraumatic Osteoarthritis in the Porcine Knee After Anterior Cruciate Ligament Surgery

Background: Posttraumatic osteoarthritis (PTOA) is a common sequela of anterior cruciate ligament (ACL) injury, even when surgical treatment is selected. The effect of patient sex on cartilage health after ACL injury and surgical treatment has been less studied. Purpose/Hypothesis: The study objective was to compare the macroscopic cartilage damage that develops after ACL surgery in male and female Yucatan minipigs. It was hypothesized that after ACL surgery, the macroscopic cartilage damage of the tibiofemoral joints from female animals would be greater than that from male animals. Additionally, it was hypothesized that the effect of sex on the macroscopic cartilage damage would depend on surgical treatment. Study Design: Controlled laboratory study Methods: Twelve-month follow-up data were obtained for 55 adolescent Yucatan minipigs (22 female/33 male) that were randomized to 1 of 3 experimental groups: no treatment (ACL transection [ACLT]), ACL reconstruction, and bridge-enhanced ACL restoration. The Osteoarthritis Research Society International guidelines were used to determine a standardized macroscopic cartilage damage score on 5 surfaces of the knee joint. Results: Females had significantly worse mean total macroscopic cartilage damage scores on the surgical side (adjusted P value [P adj] = .04) and significantly better scores on the contralateral side (P adj = .01) when compared with males. The trochlear damage scores were also significantly worse in females for surgical limbs (P adj = .009) and significantly better for the contralateral limbs (P adj < .001) when compared with males. Although there were no significant differences in total macroscopic cartilage damage scores between sexes within treatment groups on the surgical limbs (ACLT, P adj = 0.45; ACL reconstruction, P adj = .56; bridge-enhanced ACL restoration, P adj = .23), the mean trochlear scores on the surgical limb of females were significantly worse than those of the males in the ACLT group (P adj = .003). Conclusion: Mean total macroscopic cartilage damage scores of Yucatan minipigs were significantly worse in females than males, regardless of treatment. These differences were predominantly found in the trochlear scores across all treatment groups. Clinical Relevance: These data suggest that patient sex could be more influential in the progression of PTOA than surgical treatment after ACL injury. Identifying factors responsible for this discrepancy may prove valuable to identify targets to slow PTOA progression in male and female ACL-injured populations.

Cyclic loading regime considered beneficial does not protect injured and interleukin-1-inflamed cartilage from post-traumatic osteoarthritis

Injurious overloading and inflammation perturbate homeostasis of articular cartilage, leading to abnormal tissue-level loading during post-traumatic osteoarthritis. Our objective was to gain time- and cartilage depth-dependent insights into the early-stage disease progression with an in vitro model incorporating for the first time the coaction of (1) mechanical injury, (2) pro-inflammatory interleukin-1 challenge, and (3) cyclic loading mimicking walking and considered beneficial for cartilage health. Cartilage plugs (n = 406) were harvested from the patellofemoral grooves of young calves (N = 6) and subjected to injurious compression (50% strain, rate 100%/s; INJ), interleukin-1α-challenge (1 ng/ml; IL), and cyclic loading (intermittent 1 h loading periods, 15% strain, 1 Hz; CL). Plugs were assigned to six groups (control, INJ, IL, INJ-IL, IL-CL, INJ-IL-CL). Bulk and localized glycosaminoglycan (GAG) content (DMMB assay, digital densitometry), aggrecan biosynthesis (35S-sulfate incorporation), and chondrocyte viability (fluorescence microscopy) were assessed on days 3–12. The INJ, IL, and INJ-IL groups exhibited rapid early (days 2–4) GAG loss in contrast to CL groups. On day 3, deep cartilage of INJ-IL-CL group had higher GAG content than INJ group (p < 0.05). On day 12, INJ-IL-CL group showed more accumulated GAG loss (normalized with control) than INJ-IL group (average fold changes 1.97 [95% CI: 1.23–2.70]; 1.66 [1.42–1.89]; p = 0.007). Aggrecan biosynthesis increased in CL groups on day 12 compared to day 0. Despite promoting aggrecan biosynthesis, this cyclic loading protocol seems to be beneficial early-on to deep cartilage, but later becoming incapable of restricting further degradation triggered by marked but non-destructive injury and cytokine transport.

The Role of Mechanically-Activated Ion Channels Piezo1, Piezo2, and TRPV4 in Chondrocyte Mechanotransduction and Mechano-Therapeutics for Osteoarthritis.

Mechanical factors play critical roles in the pathogenesis of joint disorders like osteoarthritis (OA), a prevalent progressive degenerative joint disease that causes debilitating pain. Chondrocytes in the cartilage are responsible for extracellular matrix (ECM) turnover, and mechanical stimuli heavily influence cartilage maintenance, degeneration, and regeneration via mechanotransduction of chondrocytes. Thus, understanding the disease-associated mechanotransduction mechanisms can shed light on developing effective therapeutic strategies for OA through targeting mechanotransducers to halt progressive cartilage degeneration. Mechanosensitive Ca2+-permeating channels are robustly expressed in primary articular chondrocytes and trigger force-dependent cartilage remodeling and injury responses. This review discusses the current understanding of the roles of Piezo1, Piezo2, and TRPV4 mechanosensitive ion channels in cartilage health and disease with a highlight on the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA.

The role of arthroscopic debridement in the treatment of osteochondral lesions of the talus in the athlete

<h2>ABSTRACT</h2> Arthroscopic debridement (AD) is the most common procedure in treating cartilage lesions. However, despite its comprehensive implementation in the surgical treatment of osteochondral lesions of the talar dome (OLT) during the last century, its practice was abandoned, preferring newer techniques, and is currently omitted in most treatment algorithms. Up to date, no conclusive evidence exists regarding the superiority of bone marrow stimulation over AD, and evidence continues to be scarce on its implementation. AD represents an easy, inexpensive, technically low-demanding procedure, with potential benefits due to its rapid rehabilitation, the lack of donor-site morbidity, and without compromising the subchondral (SC) plate and bone. The SC plate and bone have been acknowledged as essential structures for cartilage health and quality of the surgical repair, participating in the load transmission of the ankle joint and linking biochemically through transport pathways with the overlying hyaline cartilage. AD alone is an OLT treatment option with potential benefits for the athlete, especially in partial-thickness cartilage injuries and non-cystic contained International Cartilage Repair Society grade III-IV OLT less than 10 mm² in size and 5 mm in depth. Additionally, AD alone can represent an appealing option for athletes looking for symptomatic relief and a fast return to sports during the season.

The Effect of Patellar Surface Morphology on Subchondral Bone Alignment When Matching Patellar Osteochondral Allografts to the Central Ridge of the Patella

Background: Cartilage transplants in the patellofemoral joint have demonstrated lower success rates than in the femoral condyles. This is likely related to the more complex morphology and biomechanics of the joint. While previous studies have evaluated cartilage surface matching and congruence, little work has been done to study the associated subchondral bone congruency in these grafts. Purpose: To determine if differences in patellar morphology play a role in the alignment of the donor patellar osteochondral allograft subchondral bone with the native patellar subchondral bone. Study Design: Controlled laboratory study. Methods: A total of 20 (10 Wiberg I and 10 Wiberg II/III) fresh-frozen human patellae were designated as recipients and size-matched to both a Wiberg I and a Wiberg II/III patellar donor. A 16-mm osteochondral allograft transplant to the central ridge of the patella was performed in random order with each matched donor. Transplanted patellae underwent a nano—computed tomography (nano-CT) scan, were digitally reconstructed, and were superimposed on the initial nano-CT scan of the native recipient patella. MATLAB was used to determine the surface height deviation between the native and donor subchondral bone surfaces. DragonFly 3-dimensional imaging software was used to measure subchondral bone step-off heights at the native-donor interface. Differences between matched and unmatched grafts were compared using a 2-way analysis of variance and the Sidak post hoc test. Results: Subchondral bone surface deviation did not differ between Wiberg matched and unmatched allografts. The step-off height was significantly greater in unmatched (1.38 ± 0.49 mm) compared with matched (1.14 ± 0.52 mm) plugs (P = .015). The lateral quadrant step-off differed between matched (0.89 ± 0.43 mm) and unmatched (1.60 ± 0.78 mm) grafts (P = .007). Conclusion: While unmatched Wiberg patellar osteochondral allograft implantation did not result in significantly different subchondral bone surface height deviations, there was a significant difference in the circumferential subchondral bone step-off height in the lateral quadrant. Further investigation using finite element analysis modeling will help determine the role of subchondral bone surface on shear and compression force distributions in these areas. Clinical Relevance: Given that subchondral bone stiffness and morphology play a role in cartilage health, subchondral bone congruency may play a role in graft survival. Understanding how this congruency plays a role in cartilage force distribution will help surgeons improve the long-term success of osteochondral allograft transplants.

Quantifying Asymmetry Between Medial and Lateral Compartment Knee Loading Forces Using Acoustic Emissions.

Osteoarthritis is the most common type of knee arthritis that can be affected by excessive and compressive loads and can affect one or more compartments of the knee: medial, lateral, and patellofemoral. The medial compartment tends to be the most vulnerable to injuries and research suggests that a better understanding of the medial to lateral load distribution conditions could provide insights to the quantitative usage of knee compartments in activities of daily life. Prior to study in an osteoarthritic clinical population which may present with various complicating anatomical and physiological changes, we investigate knee acoustical emissions of able-bodied individuals during a varying width squat exercise which simulates loading asymmetries that would typically be seen in this clinical population. To that end, we present a novel method to quantify the directional bias of asymmetry between the medial and lateral compartment knee joint load in healthy individuals by recording knee acoustical emissions and analyzing them using a deep neural network in a subject independent model. We placed four miniature contact microphones on the medial and lateral sides of the patella on both the left and right leg. We compared the handcrafted audio features with the automated features extracted from the convolutional autoencoder which is an unsupervised model that learns the comprehensive representation of the input to determine whether these automated features can better represent the signal's characteristic in regard to the structural asymmetry of the knee joint. The input to the convolutional auto encoder (CAE) is a time-frequency representation and different types of these images such as spectrogram and scalogram are compared. We alsocompared the multi-sensor fusion approach with the performance of a single sensor to determine the robustness of using multiple sensors. Using a representation learning based approach, we developed a subject independent classification model capable of classifying the asymmetry of the medial and lateral joint load across subjects (accuracy = 83%). The result indicates that wavelet coherence which is the time-frequency correlation of two signals using a wavelet transform yields the best accuracy. These findings suggest that acoustic signals could potentially quantify the direction of medial to lateral load distribution which would broaden the implications for wearable sensing technology for monitoring cartilage health and factors responsible for cartilage breakdown and assessing appropriate rehabilitation exercises without overloading on one side.