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The aim of the study was to verify the effects of foot progression angle (FPA) modification during walking on the internal moments of the ankle and knee joints in individuals with knee osteoarthritis (OA). Biomechanical changes such as increased knee adduction moment (KAM) during walking are known to be involved in the development and severity of knee OA. Although various FPA modifications during gait have been applied to reduce peak KAM, few studies have investigated the effects of applying toe-in or toe-out walking modifications for knee OA on peak KAM and three-dimensional (3D) moments of the ankle joint. Kinetic moment variables were acquired from 35 individuals with medial knee compartment OA. A 3D motion analysis system and two force platforms were used to acquire KAM and 3D moments of both ankle joints during gait. Visual3D was used to obtain final moment data for statistical processing. Repeated-measures analysis of variance with Bonferroni adjustment was used to compare kinetic and kinematic values for each FPA walking condition. There was a significant decrease (p < 0.01) in first peak KAM when walking with an internal rotation foot position compared to normal foot position walking. Also, there was a significant decrease (p < 0.01) in second peak KAM when walking with an external rotation foot position compared to normal foot position walking. Compared to a normal foot position, peak ankle inversion moment of the external rotation foot position walking showed a significant decrease (p < 0.05). There were no interactive effects between FPA condition and limb sides for any KAM values (p > 0.05). The results showed no significant increase in the ankle joint moment value during gait for FPA modification conditions. Thus, the clinical implications of this study suggest that modification of the FPA in patients with OA to reduce KAM does not negatively impact the 3D ankle moments. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti‐nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA‐related pain, among other conditions. Data from 12 Phase I‐III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab concentration‐time profiles and assess the covariates' effect on fasinumab pharmacokinetic parameters. Participants received single or repeated fasinumab doses intravenously (IV)/subcutaneously (SC), based on body weight (0.03‐1 mg/kg IV or 0.1‐0.3 mg/kg SC)/fixed dose (9‐12 mg IV or 1‐12 mg SC). Fasinumab concentration‐time data following IV and SC administration in healthy volunteers and patients with OA‐related pain were adequately described by a 2‐compartment model. Bioavailability increased with higher doses; estimated at 55.1% with 1 mg SC dose, increasing in a greater‐than‐proportional manner above this. Body weight had the largest predicted impact on fasinumab steady‐state exposures, participants at the 5th and 95th percentiles had a 43%‐45% higher/22%‐23% lower exposure versus reference, respectively. Other covariates had small but clinically irrelevant impacts. [ABSTRACT FROM AUTHOR]

In patients with medial knee osteoarthritis (OA), medial meniscus extrusion during gait is aggravated by mechanical stress, such as knee adduction moment (KAM). Conversely, the decrease in the range of knee rotation during stance phase is also one of the important issues in early knee OA, whereas the correlation between medial meniscus extrusion and knee rotation during gait are unclear. To investigate the correlation between increase in medial meniscus extrusion and range of knee rotation during gait in patients with early- and late-stage of knee OA. Forty patients with medial knee OA were enrolled and divided into early- and late-OA group by Kellgren-Lawrence grading scale. During gait tasks, the extent of medial meniscus extrusion was measured using ultrasonography and kinetic/kinematic data were measured using three-dimensional motion analysis system. The correlation between medial meniscus extrusion and the range of knee rotation or KAM were evaluated in the overall, early-, and late- OA groups. A significant negative correlation was observed between an increase in medial meniscus extrusion and range of knee rotation angle in early-OA group only. However, an increase in medial meniscus extrusion significantly correlated with the second KAM peak in the overall and early-OA groups. The decrease in range of knee rotation during stance phase may be associated with the increase in medial meniscus extrusion during gait in patients with early knee OA. • Assessed correlation of medial meniscus extrusion with knee rotation during gait. • Meniscus extrusion aggravated with restriction of knee rotation in early knee OA. • Meniscus extrusion was not correlated with knee rotation in late knee OA. • Meniscus extrusion correlated with knee adduction moment peak in knee OA. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare three-dimensional kinematic of the trunk, pelvis, hip, and knee during the single-leg squat and hip torque in individuals with and without isolated patellofemoral osteoarthritis (PFOA). Patients and methods: This cross-sectional study evaluated trunk, pelvis, hip, and knee kinematics at 30°, 45°, and 60° knee flexion during the single-leg squat using the Vicon motion capture and analysis system, the Nexus System 2.1.1, and 3D Motion Monitor software. Sixteen individuals (8 males, 8 females; mean age: 49.3±6.2 years; range 40 to 61 years) participated in the study, of which eight were PFOA patients and eight were healthy controls. Isometric hip abductor, extensor, and external rotator torques were evaluated using a handheld dynamometer. Results: The PFOA group exhibited greater hip adduction at 30° (p=0.008), 45° (p=0.005), and 60° (p=0.008) knee flexion in the descending phase of the single-leg squat, as well as at 60° (p=0.009) and 45° (p=0.03) knee flexion in the ascending phase. No significant differences were found between groups for other kinematic variables (p>0.05). The PFOA group exhibited lower isometric hip abductor (p=0.02), extensor (p<0.001), and external rotator (p=0.007) torques. Conclusion: Individuals with PFOA exhibited excessive hip adduction that could increase stress on the lateral patellofemoral joint at 30°, 45°, and 60° knee flexion during the single-leg squat and exhibited weakness of the hip abductors, extensors, and external rotators in comparison to healthy controls. [ABSTRACT FROM AUTHOR]

BACKGROUND: Measurements of hip abduction (ABD) and adduction (ADD) are important in strength and conditioning as well as in clinical practice. However, there is no clear consensus on how ABD and ADD compare in strength in different populations. OBJECTIVE: The aim was to perform a quantitative synthesis of comparisons between the isometric strength of ABD and ADD in different populations. METHODS: ABD and ADD strength data were collected and pooled mean values for ABD:ADD strength ratio were calculated and expressed as standardized mean differences. Forty studies of healthy adults, 5 studies of healthy older adults and 14 studies of adults with various musculoskeletal injuries were included in the analysis. RESULTS: Healthy (non-athletic) males, healthy older adults, and adults with hip and groin pathologies or osteoarthritis tend to have the same ADD and ABD strength; male athletes tend to have a stronger ADD compared with ABD; healthy females and adults with patellofemoral pain tend to have a stronger ABD compared with ADD. CONCLUSIONS: These results can serve as a database to help compare and interpret measurements of ADD and ABD strength ratio in different populations. [ABSTRACT FROM AUTHOR]

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM–OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control. [ABSTRACT FROM AUTHOR]

Background: Lateral wedge insoles (both standalone and those incorporating individualized arch support) have been frequently studied for the effects on knee joint loading and pain in people with knee osteoarthritis. It has been shown that many people who use these insoles do not obtain the intended biomechanical effect, and thus may not experience a clinical benefit. The ability to identify biomechanical responders to lateral wedge insoles before research or clinical intervention is an important objective for efficient resource use and optimizing patient outcomes. The purpose of our exploratory, hypothesis-generating study was to provide an initial assessment of variables that are associated with the biomechanical response to lateral wedge insoles in people with knee osteoarthritis. Methods: We collected a number of demographic (age, sex, body mass index, foot posture), clinical (knee pain, foot pain, radiographic disease severity), and walking-related (speed, knee alignment, frontal plane subtalar movement, and foot rotation) outcomes from 53 individuals with painful, radiographically-confirmed knee osteoarthritis. The walking-related outcomes were obtained using equipment both from the research laboratory and the clinical setting. We used logistic regression to generate predictive models to determine candidate variables associated with a reduction in the knee adduction moment during walking – a surrogate for tibiofemoral load distribution, and a known biomechanical risk factor for osteoarthritis progression – with the use of standalone and arch-supported lateral wedge insoles. Three different response thresholds (2%, 6%, and 10% reductions in the knee adduction moment) were used. Results: In general, biomechanical responders were those who walked faster, were female, had less varus alignment, and had less severe radiographic severity. Findings were similar between the standalone and arch-supported lateral wedge insoles, as well as between models using the laboratory-derived or clinically-available measures of walking performance. Conclusions: Our hypothesis-generating study provides valuable information that will inform future research into the efficient and effective use of lateral wedge insoles in the conservative management of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective: Our previous studies revealed that normal synovial exosomes promoted chondrogenesis, and microRNA (miR)-19b-3p independently related to osteoarthritis (OA) risk. Subsequently, this study intended to further explore the effect of OA fibroblast-like synoviocyte (OA-FLS) exosomal miR-19b-3p on OA ferroptosis and its potential mechanisms. Methods: Interleukin (IL)-1b-stimulated chondrocytes and medial meniscus surgery were used to construct the OA cellular model and the OA rat model, respectively. OA-FLS exosomes with/without miR-19b-3p modification were added to the IL-1bstimulated chondrocytes and OA rat models, followed by directmiR-19b-3p mimic/ inhibitor transfection with/without SLC7A11 overexpression plasmids. miR-19b-3p, ferroptosis-related markers (malondialdehyde (MDA), glutathione (GSH)/oxidized glutathione (GSSG), ferrous ion (Fe2+), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4)), mitochondrialmembrane potential (MMP), and reactive oxygen species (ROS) levels were detected. Results: Enhanced ferroptosis reflected by dysregulated ferroptosis-related markers, a reduced MMP, and an increased ROS was observed in cartilage tissues from OA patients vs. controls, IL-1b-stimulated chondrocytes vs. normal ones, and OA rat models vs. sham, so did miR-19b-3p. OA-FLS exosomes promoted MDA, Fe2+, ACSL4, and ROS but reduced cell viability, GSH/GSSG, GPX4, SLC7A11, and MMP in IL-1β-stimulated chondrocytes, whose effect was enhanced by miR-19b-3p mimics and attenuated by miR-19b-3p inhibitors. miR-19b-3p negatively regulated SLC7A11 and directly bound to SLC7A11 via luciferase reporter gene assay. Furthermore, SLC7A11 overexpression weakened miR-19b-3p mimics' effect on ferroptosis-related markers, MMP, or ROS in IL-1b-stimulated chondrocytes. OA-FLS exosomes also induced cartilage damage and ferroptosis in OA rats whose influence was tempered by miR-19b-3p inhibitors. Conclusion: OA-FLS exosomal miR-19b-3p enhances cartilage ferroptosis and damage by sponging SLC7A11 in OA, indicating a potential linkage among synovium, cartilage, and ferroptosis during the OA process. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common disease of the first carpo-metacarpal (CMC I) joint. Biomechanical factors promoting OA are the shape of the CMC I-joint, being a biconcave-convex saddle joint with high mobility and the increased instability caused by joint space narrowing, ligamentous laxity, and direction of force transmission of the abductor pollicis longus (APL) tendon during adduction. The closing wedge osteotomy of the base of the first metacarpal is joint preserving treatment option. We combine this closing wedge osteotomy with a ligamentoplasty to stabilize the joint. In this manuscript, we provide a detailed description of the indication, discuss biomechanical aspects and the surgical technique in detail. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1β-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment. Clinical trial registration: Not applciable. [ABSTRACT FROM AUTHOR]

Purpose. Sit-to-stand (STS) is functionally more critical for the independency of people with osteoarthritis (OA). During STS, OA people experience a lot of pain from high sagittal torque. This study investigated the effect of toe-out (T-O) and toe-in (T-I) on knee adduction moment (KAM) and knee flexion moment (KFM) during STS in moderate knee osteoarthritis (KOA) and healthy age-matched people. Methods. In this cross-sectional study, 19 volunteers with moderate KOA (KOA group) and 15 age-matched healthy individuals (control group) participated. KAM, KFM, peak times, and terminal knee flexion angle were measured using a motion analysis system during STS in normal foot progression angle (FPA), 10° of T-O, and 10° of T-I. The repeated-measures ANOVA was used to determine the effects of group and FPA condition and their interactions on the knee kinetic and kinematic parameters. Results. T-I reduced the peak KAM significantly in both groups (p = 0.025 and p = 0.05, respectively). Irrespective of the group, T-O and T-I significantly reduced the peak time of KAM and KFM (p = 0.003 and p = 0.035, respectively). People with KOA had significantly higher terminal knee flexion than healthy subjects in all FPA conditions. Conclusions. Ten degrees of toe-in reduced KAM in healthy and KOA people during STS; it may effectively diminish the medial knee contact force in people with KOA. [ABSTRACT FROM AUTHOR]

Decreasing an external hip adduction moment (HAM) impulse during stance is important to prevent the progression of hip osteoarthritis. A hip adduction angle (HAA) during walking influences the HAM impulse. Although a wider step-width (WS) gait is a gait modification to decrease a peak HAM, no study has reported the HAM impulse and HAA. We investigated whether the HAA influences the peak HAM and HAM impulse during WS gait. Twenty-six healthy young adults walked with normal step-width (NS) and WS comfortably. They were not instructed about hip adduction motion during gait, and the peak HAM, HAM impulse, HAA, and other gait parameters were evaluated using a 3D motion capture system. The participants were divided into two groups according to the HAA size during WS gait. The percentage reduction of HAM variables (the WS condition relative to the NS condition) and other gait parameters were compared between the groups. No difference in gait parameters was found between the groups. The percentage reduction of the HAM impulse in participants with smaller HAA was significantly higher than that in participants with larger HAA (14.5 % vs. 1.6 %, p < 0.01). Also, during normal step-width gait, the large HAA group showed a significantly larger HAA compared to the small HAA group (about 3°). Participants with smaller HAA could decrease the HAM impulse more effectively during WS gait compared with those with larger HAA. Thus, the HAA would influence the HAM impulse reduction effect on the WS gait. We recommend paying attention to the HAA to decrease the HAM with the WS gait. • A relationship between hip adduction moment (HAM) and angle (HAA) was investigated. • Subjects with smaller HAA during wider step-width gait could reduce HAM effectively. • Subjects with larger HAA showed large HAA during normal step-width gait similarly. • We need to focus on HAA in gait modification with wider step-width to reduce HAM. [ABSTRACT FROM AUTHOR]

Objective: In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis. Methods: We performed 2‐sample MR using summary‐level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome‐wide association using the UK Biobank, and for site‐specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity–osteoarthritis relationship. Results: Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site‐specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (Pnonlinear = 0.003). Conclusion: Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints. [ABSTRACT FROM AUTHOR]

Background: High tibial osteotomy (HTO) reduces the load distribution of the medial compartment by modifying leg alignment. Knee adduction moment (KAM), a surrogate measure of dynamic loading in the knee joint, decreases after HTO. However, leg alignment does not fully account for KAM. Purpose: To assess the association between the pelvis-knee-ankle angle (PKA), a novel radiographic parameter reflecting leg alignment and pelvic width, and KAM and patient-reported outcomes after HTO. Study Design: Cross sectional study; Level of evidence, 3. Methods: PKA is the angle between the line from the midpoint of the anterior superior iliac spine to the center of the knee joint and the mechanical axis of the tibia. In this study, 54 patients with medial compartment knee osteoarthritis and varus alignment who underwent 3-dimensional gait analysis preoperatively and 2 years after medial open-wedge HTO were evaluated. The primary outcomes were hip-knee-ankle angle (HKA), PKA, KAM peaks, and Knee Society Score (KSS). Single and multivariate regression analysis including PKA and KAM peaks as well as other demographic and radiologic factors was performed. Results: HKA was weakly correlated with the first peak KAM (r = −0.33; P <.01) and second peak KAM (r = −0.27; P =.01) before HTO, but not significantly correlated after HTO. PKA was moderately correlated with the first peak KAM (r = 0.45; P <.01) and second peak KAM (r = 0.45; P <.01) before HTO and with the first peak KAM (r = 0.51; P <.01) and second peak KAM (r = 0.56; P <.01) after HTO. Multivariate linear regression revealed that postoperative PKA was still associated with the KAM peaks after HTO. Only postoperative PKA was correlated with the KSS satisfaction subscale (r = −0.30; P =.03). Conclusion: Although HKA was not correlated with KAM peaks after HTO, PKA was significantly correlated with KAM peaks in patients with varus knee osteoarthritis after HTO. [ABSTRACT FROM AUTHOR]

Using insoles to modify walking biomechanics is of keen interest for the treatment of medial-compartment knee osteoarthritis. So far, insole interventions have focused on reducing the peak of the knee adduction moment (pKAM) and have led to inconsistent clinical outcomes. This study aimed to evaluate the changes in other gait variables related to knee osteoarthritis when patients walk with different insoles to provide insights into the necessity to enlarge the biomechanical analyses to other variables. Walking trials were recorded for 10 patients in four insole conditions. Changes among conditions were computed for six gait variables, including the pKAM. The associations between the changes in pKAM and the changes in the other variables were also assessed individually. Walking with different insoles had noticeable effects on the six gait variables, with high heterogeneity among patients. For all variables, at least 36.67% of the changes were of medium-to-large effect size. The associations with the changes in pKAM varied among variables and patients. In conclusion, this study showed that varying the insole could globally influence ambulatory biomechanics and that limiting measurement to the pKAM could lead to an important loss of information. Beyond the consideration of additional gait variables, this study also encourages personalized interventions to address inter-patient variability. [ABSTRACT FROM AUTHOR]

One of the recommendations for individuals with knee osteoarthritis (OA) is the use of specific footwear, such as sturdy or cushioned shoes. However, the long-term use effects of using cushioned shoes on the pain and spatiotemporal gait parameters in individuals with knee OA are yet to be reported. We therefore aimed to compare the efficacy of cushioned sport footwear versus sham shoes on motor functions, pain and gait characteristics of individuals with knee OA who used the shoes for 3 months. In a double-blinded study, we provided 26 individuals with knee OA with cushioned sport shoes and 12 individuals with knee OA with similar sport shoes without cushioning for 3 months. The gait analysis, the timed up and go (TUG) test and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) were conducted and the pain levels were measured at the baseline, 1 month, and 3 months after the baseline. We found that the cushioned shoes reduce the amount of pain (based on WOMAC) in the affected knee and increase functionality in the research group, but not in the control group. Gait velocity and cadence were increased in both groups. Gait spatiotemporal parameters and their symmetry were unaffected during the intervention. We conclude that the use of cushioned shoes should be recommended to individuals with knee OA for alleviating pain. [ABSTRACT FROM AUTHOR]

This study examined the effects of obesity on cartilage mechanics and longitudinal failure probability at the medial tibiofemoral compartment, using combined musculoskeletal simulation and probabilistic failure modelling approaches. The current investigation examined twenty obese females (BMI > 30.0 kg/m2) and 20 healthy weight (BMI < 25.0 kg/m2) females. Walking kinematics were obtained via an 8-camera optoelectric system, and a force plate was used to collect ground reaction forces. Musculoskeletal simulation and probabilistic failure modelling were utilized to explore medial tibiofemoral forces and cartilage probability. Comparisons between groups were undertaken using linear mixed-effects models. Net peak cartilage forces, stress and strain were significantly larger in the obese group (force = 2013.92 N, stress = 3.03 MPa & strain = 0.25), compared to health weight (force = 1493.21 N, stress 2.26 MPa & strain = 0.19). In addition, medial tibiofemoral cartilage failure probability was also significantly larger in the obese group (42.98%) compared to healthy weight (11.63%). The findings from the current investigation show that obesity has a profoundly negative influence on longitudinal medial knee cartilage health and strongly advocates for the implementation of effective weight management programs into long-term musculoskeletal management strategies. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone. [ABSTRACT FROM AUTHOR]

This study aimed to compare a biaxial ankle-foot orthosis (AFO) with a lateral wedge insole in terms of the biomechanical and clinical outcomes in individuals with knee osteoarthritis. A cross-over randomized design was used where 31 individuals (25 females and six males, mean age of 52.19 ± 4.12 years) with knee osteoarthritis wore each intervention for two weeks with two weeks washout period. Three-dimensional kinematic and kinetic data and clinical outcomes were collected to evaluate the effects of each intervention on knee adduction moment (KAM), pain, stiffness, and function. Both orthoses significantly improved pain by 17 and 22%, function by 11 and 14%, the first peak KAM by 15.7 and 19.2%, the second peak KAM by 10.4 and 16.7%, and KAM impulse by 14.8 and 22.2%, respectively. However, the biaxial AFO significantly reduced the KAM and improved function compared to the lateral wedge insole (p < 0.01). The results of this study have shown that both orthoses have a potential role in the conservative management of medial knee osteoarthritis. The biaxial AFO proved statistically better at improving function and KAM; though these differences do not seem to be clinically significant. Orthotic interventions have been reported to be effective in the management of medial knee osteoarthritis. Lateral wedge insole and biaxial ankle-foot orthosis (AFO) are effective in the improvement of pain, function, and knee adduction moment (KAM) in people with medial knee osteoarthritis. The biaxial AFO, compared with lateral wedge insole, contributes to statistically more improvement of function and KAM. However, these differences do not seem to be clinically significant. [ABSTRACT FROM AUTHOR]

As the modern golf swing has changed, the incidence of knee pain in professional golfers is increasing. For those with previous knee injuries, developing a golf-swing modification that reduces knee loading may be necessary to recover performance after injury. The purpose of this study was to test whether ball position modification reduces knee joint load in a golf swing. Thirteen male professional golfers participated in the study. Golf swings were captured using a three-dimensional motion capture system and two force platforms, with conditions for self-selected ball position and eight additional ball positions. Knee internal rotation and adduction moments were calculated. The length of one golf ball (4.27 cm) backward ball position (closer to the golfer) significantly reduced the peak internal rotation moment of the lead knee (-13.8%) (p < 0.001) and the length of one golf ball (4.27 cm) away from the target ball position significantly reduced the peak adduction moment of the lead knee (-11.5%) (p < 0.001) compared with that of the self-selected ball position. Based on these observations, we conclude that the backward ball position modification might be suggested for golfers with anterior cruciate ligament injuries, and the away from the target modification might be suggested for golfers with medial compartment knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Objective: This study aimed to investigate the effects of a 6-wk proprioceptive neuromuscular facilitation stretching on pain, proprioception, joint range of motion, and joint moments during stair ascending among older adults with knee osteoarthritis. Design: This study is a randomized, controlled, and assessor-blinded trial. Thirty-six older adults with knee osteoarthritis were randomly assigned to the proprioceptive neuromuscular facilitation and the control groups. They received proprioceptive neuromuscular facilitation stretching and health lecture series, respectively, for 6 wks. Final data analysis included 14 participants of the proprioceptive neuromuscular facilitation group and 13 of the control group. Pain score, joint proprioception, range of motion, and joint moments during stair ascending were measured before and after the stretching. Two-way (group by time) analysis of variance with repeated measures was used to evaluate stretching effects. Results: Significant interactions were detected in pain score, joint proprioception, external knee adduction moment, and external knee extension moment. Compared with week 0, the pain score, joint proprioception threshold, and external knee adduction moment decreased, whereas the external knee extension moment increased among older adults in the proprioceptive neuromuscular facilitation group at week 7. Conclusions: Proprioceptive neuromuscular facilitation could be recommended as one of the clinical treatments for knee osteoarthritis to relieve pain, improve proprioception, and balance load distribution between medial and lateral compartments at the knee. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common type of arthritis, affecting millions of people around the world. Angiopoietin-2 (Angpt-2) has a role in the development of chronic inflammatory diseases. We aimed to assess the serum Angpt-2 levels in knee OA patients and to investigate the association of Angpt-2 gene polymorphism(rs3020221 C/T) with knee OA susceptibility and severity. Angiopoietin-2(rs3020221C/T) gene polymorphism was identified in 254 knee OA patients and 227 healthy controls using real-time polymerase chain reaction. Serum Angpt-2 was measured using ELISA. The Arabic version of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Kellgren-Lawrence (KL) grading score were used to assess the clinical and radiological severity of OA and their relationship with Angpt-2(rs3020221C/T) gene polymorphism was investigated. Serum Angpt-2 levels were significantly higher in knee OA patients than in the controls (P =.001). OA patients with C/T genotype had a four times greater risk of developing OA than other genotypes (OR = 4.39, 95% CI = 2.85–6.76). Additionally, the T allele presented more in OA patients 224/508 (44%) with two times risk of developing OA (OR = 1.86, 95% CI = 1.43–2.43, p =.001). Angpt-2 SNP (rs3020221C/T) genotype C/T was significantly associated with elevated serum Angpt-2 levels (14.15 ± 5.62 ng/ml). The serum Angpt-2 levels are significantly elevated in OA patients and Angpt-2 gene polymorphism (rs3020221 C/T) may be a risk factor for OA development and both are associated with the severity of knee OA. Carriers of the C/T genotype have a significantly higher serum Angpt-2 levels and a greater risk of developing OA. [ABSTRACT FROM AUTHOR]

The knee unloader brace can change loading on knee which may be effective in reducing symptoms and progression of disease in people with knee osteoarthritis. The purpose of this study was to evaluate the effect of a new knee brace during walking in a patient with medial compartment knee osteoarthritis. Two brace types were used: new brace and conventional brace. A pneumatic cuff of novel brace was fitted in the bottom of the medical slipper that was connected to the cuff section of the knee through the tube. After the knee brace is deployed, its force can vary in different stages of the gait. During the heel strike, the weight of the cuff is compressed on the floor, causing the air to flow inside it and entering the volume of air into the knee pad. The results of using this pneumatic knee brace compared with conventional knee braces on a patient showed that in both cases, the open and closed palatal pump, the adduction moment and ROM was decreased in the stance phase. But the three-point knee pressure, however, was less effective in reducing the adduction moment but also reduced the knee ROM. Using novel brace can eliminate the patient's need for painful and costly surgery to reduce the symptoms of osteoarthritis. [ABSTRACT FROM AUTHOR]

Purpose: Several cytokines and growth factors start and progress the destruction process of joint hyaline cartilage and fibrosis formation. Captopril is classified as an Angiotensin-converting enzyme inhibitor in which several studies revealed that captopril significantly decreases fibrosis formation in some organs like the liver, heart, and kidney. This study aimed to evaluate the use of captopril in reducing the possibility of arthrofibrosis and osteoarthritis in an animal model. Method: In this in-vivo animal model study, the anterior cruciate ligament of 24 rabbits was transected to induce osteoarthritis and arthrofibrosis. The control group contained 11 rabbits and the second group consisted of 13 rabbits. The second group was treated with 10 mg/ kilogram/day captopril through a nasogastric tube. The control group was treated with normal saline in the same way. Cartilage damage and osteoarthritis were evaluated by Osteoarthritis Research Society International (OARSI) scoring system. After 30 days, animals were sacrificed, and arthrofibrosis and cartilage damage were evaluated microscopically and macroscopically. Results: According to macroscopic and microscopic evaluation, captopril dramatically reduced arthrofibrosis formation based on visual scoring and the Masson trichrome staining system. Cartilage damage was lower in the intervention group compared to the control group. Conclusions: Captopril is an angiotensin-converting enzyme inhibitor that demonstrated to significantly decreases the possibility of arthrofibrosis. Although the beneficial preventive effect of captopril on osteoarthritis was not proved statistically, better results may be obtained if the route of administration or drug dosage is changed. [ABSTRACT FROM AUTHOR]

Intra-articular injections of glucocorticoids (GC) or hyaluronic acid (HA) are commonly used interventions for patients suffering from knee osteoarthritis (OA). Both substances are combined to achieve a chondroprotective and anti-inflammatory effect. Clinical studies have shown benefits, but data on the cellular level are still lacking. This study aimed to investigate the effect of the GC triamcinolone hexacetonide, HA, and a mix of both substances on cytokine-treated chondrocytes in vitro. Chondrocytes isolated from human articular cartilage were seeded on 6- and 24-well plates. Mimicking OA's inflammatory state, cells were treated with IL-1β and IL-17 for six days, whereby, after three days, test substances (10%) were added to the culture medium. Chondrocytes were analyzed on days three and six concerning their actin polymerization, expression of anabolic and catabolic genes, metabolic activity, cytokine release, and reactive oxygen species (ROS). Adding HA or GC/HA to the inflammatory culture medium increased the metabolic activity of chondrocytes, while groups containing GC reduced catabolic gene expression and the release of TNF-α. In addition, enhanced F-actin content was shown supplementing HA or GC/HA to the culture medium. Supplementing GC with HA leads to an anti-inflammatory and chondroprotective effect by diminishing the side effects of GC supplementation alone. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine associations between T1ρ relaxation times of talar and subtalar articular cartilage and commonly altered gait biomechanics and postural control outcomes in those with chronic ankle instability (CAI). Methods: Fifteen individuals with CAI (21.13 ± 1.81 yr) completed a T1ρ magnetic resonance imaging as well as a postural control and an overground gait assessment. Talocrural and subtalar cartilage was segmented manually to calculate T1ρ relaxation times. Greater T1ρ relaxation times were interpreted as decreased proteoglycan content. Pearson product–moment bivariate correlations examined the relationships between T1ρ relaxation times and the gait biomechanics and postural control outcomes. Results: Across multiple variables, worse postural control demonstrated moderate to strong associations (range, 0.433–0.642 and −0.713) with greater talar T1ρ relaxation times. At the subtalar joint, greater T1ρ relaxation times were associated with lower peak vertical ground reaction forces, lower average vertical ground reaction force loading rates, and lower peak loading rates (range, −0.438 to −0.622). At the talar dome, greater talar T1ρ relaxation times were associated with increased knee extensor moments (r = 0.457), as well as greater knee flexion (r = 0.482) and knee adduction (r = 0.407) at initial contact. Larger step spatiotemporal gait parameters also associated with greater talar and subtalar T1ρ relaxation times (range, 0.434–0.697). Conclusions: In individuals with CAI, worse postural control and altered kinematic, kinetic, and spatiotemporal outcomes demonstrate moderate to strong associations with greater talar T1ρ and/or subtalar relaxation times (i.e., less proteoglycan content). Associations between modifiable neuromechanical variables and greater T1ρ relaxation times may represent potential therapeutic interventions to mitigate ankle joint degeneration in those with CAI. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the major cause of disability, affecting over 30 million US adults. Continued research into the role of neovascularization and inflammation related to osteoarthritis in large-animal models and human clinical trials is paramount. Recent literature on the pathogenetic model of OA has refocused on low-level inflammation, resulting in joint remodeling. As a result, this has redirected osteoarthritis research toward limiting or treating joint changes associated with persistent synovitis. The overall goal of this review is to better understand the cellular and tissue-specific mechanisms of inflammation in relation to a novel OA treatment modality, Genicular Artery Embolization (GAE). This article also assesses the utility and mechanism of periarticular neovascular embolization for the treatment of OA with a particular emphasis on the balance between pro-angiogenic and anti-angiogenic cytokines, inflammatory biomarkers, and imaging changes. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with mild knee osteoarthritis are prone to induce pain and aggravation of arthritis during daily gait walking. At present, the changes in the biomechanical behavior of the internal knee joints of such patients under the gait flexion angle are not very clear. There are few reports in the literature. OBJECTIVE: Based on the proven finite element model of the mild osteoarthritis knee joint, according to the change of gait cycle and knee flexion angle, to simulate the knee flexion behavior at four angles of 0°, 10°, 20°, and 30°, and to study the stress distribution characteristics and contact area changes of femoral cartilage, tibial cartilage, and meniscus. METHODS: The material properties of the finite element model of the mild osteoarthritis knee joint were defined. The boundary conditions and the axial load were determined under different knee flexion angles. By analyzing the Mises stress, Tresca stress, and contact area of the non-bone tissue in the tibiofemoral joint, the biomechanical behavior changes inside the knee joint were studied. RESULTS AND CONCLUSION: The results of finite element analysis showed that as the knee flexion angle increased, the peak Mises stress and the peak Tresca stress on the meniscus, femoral cartilage, and tibial cartilage showed a relatively increasing trend. The total contact area of the tibiofemoral joint showed a decreasing trend, and the medial meniscus subluxation caused the lateral peak to be larger than the medial peak. Meanwhile, the contact area of the medial compartment decreased and the contact area of the lateral compartment increased. When the knee flexion angle reached 20° and 30°, the peak of Mises stress and the peak of Tresca stress appeared. Results showed that when the knee flexion angle of the mild osteoarthritis knee joint changed, the internal stress and contact area change characteristics changed because of the medial meniscus subluxation. The medial contact area decreased; the peak stress increased; and the lateral contact area increased. The peak stress increased and the increase was greater than the inside. The breakdown of the internal load balance of the joint may increase the risk of articular cartilage degeneration and promote the aggravation of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) serves as one of the most prevalent types of joint disorders and is a leading cause of symptoms of stiffness, swelling, and arthralgia. Circular RNAs (circRNAs) have been reported to participate in various cellular processes by competing with microRNAs. Meanwhile, cyclinD1 (CCND1) is a key cell cycle regulatory protein and plays a crucial role in OA progression. Nevertheless, the function of circRHOT1 in the modulation of OA progression is still obscure. Here, we explored the effect of circRHOT1 on autophagy and extracellular matrix (ECM) in OA.Methods: The expression of circRHOT1 and autophagy markers was detected in OA samples. The effect of circRHOT1 on OA was analyzed in the OA rat model. The function of circRHOT1 in the regulation of OA was assessed by CCK-8, colony formation, flow cytometry analysis, quantitative real-time PCR, Western blot analysis, and luciferase reporter gene assay in chondrocytes.Results: We observed that autophagy markers, including LC3 and beclin1, were repressed in clinical OA samples. The expression of circRHOT1 and CCND1 was induced but the miR-142-5p expression was reduced in clinical OA samples. The miR-142-5p expression was negatively correlated with circRHOT1 and CCND1, and the circRHOT1 expression was positively associated with CCND1 in clinical OA samples. Meanwhile, the apoptosis was induced in OA rats but the depletion of circRHOT1 could block the phenotype in the rats. The articular cartilage degeneration was promoted in OA rats, while the knockdown of circRHOT1 repressed the degeneration. The serum levels of CTX-II and COMP were increased in OA rats, and the silencing of circRHOT1 downregulated levels of these proteins. In addition, the expression of collagen II and aggrecan was promoted by the depletion of circRHOT1 in the OA rats. Significantly, the expression of LC3 and beclin1 was suppressed in OA rats, in which the knockdown of circRHOT1 could reverse the effect. Moreover, the depletion of circRHOT1 repressed the cell viability and proliferation but induced apoptosis of chondrocytes. The expression levels of LC3, beclin1, collagen II, and aggrecan were induced by circRHOT1 knockdown. Mechanically, circRHOT1 was able to enhance the CCND1 expression by sponging miR-142-5p in chondrocytes. The overexpression of CCND1 or the inhibition of miR-142-5p reversed circRHOT1 depletion-mediated chondrocyte phenotypes.Conclusions: Circular RNA RHOT1 enhances the CCND1 expression by sponging miR-142-5p to inhibit chondrocyte autophagy and promote chondrocyte proliferation in osteoarthritis. Our findings provided a promising therapeutic target for OA. [ABSTRACT FROM AUTHOR]

Objectives: The FTO gene has been reported as an obesity-associated gene and is also considered a risk gene for osteoarthritis (OA). However, its exact function is unclear, and there is conflicting evidence on the involvement of FTO polymorphisms in OA via obesity. The purpose of this study was to determine the effects of FTO polymorphism rs8044769 alleles on OA in the temporomandibular joint (TMJ), which is minimally affected by body weight. Materials and methods: A total of 324 TMJs (113 with OA and 211 without OA, serving as controls) from 162 Japanese patients with temporomandibular disorders and undergoing MRI examination were analyzed. Genotyping was conducted, and multivariate analysis was performed after adjusting for the effects of age, sex, body mass index, and TMJ disc abnormalities. Results: Mean age, BMI, and sex did not differ between the TMJs with OA and the TMJs without OA, but a significant difference was found for positional and dynamic disc abnormalities (P < 0.05). The allele frequency of FTO polymorphisms also differed significantly between the TMJs with OA and the TMJs without OA (P = 0.011). Moreover, logistic regression analysis showed no significant association between BMI (P = 0.581) and the occurrence of TMJOA but also indicated that the CC allele of rs8044769 is a risk factor for TMJOA (P = 0.040). Conclusions: Our results show that rs8044769 in the FTO gene might be involved in TMJOA. Clinical relevance: The present study provides a basis for a deeper understanding of the mechanism underlying degenerative skeletal diseases and the more effective selection and development of treatment strategies based on the patients' genetic characteristics. [ABSTRACT FROM AUTHOR]

Altered knee moments are common during gait in patients after anterior cruciate ligament reconstruction (ACLR). Modifiable factors that influence knee moments and are feasible to record in clinical settings such as strength and spatiotemporal values (eg, step length, step width) have not been identified in persons after ACLR. To identify strength and spatiotemporal gait values that can predict knee moments in persons after ACLR. Cross-sectional study. Laboratory. Twenty-three individuals with ACLR (14.4 ± 17.2 months post-ACLR). Peak knee-flexion and -adduction moments were measured while the participants walked at self-selected speeds. Peak isokinetic knee-extensor strength (60°/s) was recorded on a dynamometer, and spatiotemporal gait values were recorded using a pressure walkway. Pearson coefficients were calculated to examine the association of peak knee moments with strength and gait values. Variables correlated with peak knee-flexion and -adduction moments were entered into a stepwise regression model. Knee-extensor strength and step width were the strongest predictors of knee-flexion moment, accounting for 44% of the variance, whereas stance-phase time and step width were the strongest predictors of knee-adduction moment, explaining 62% of the variance. The identified spatiotemporal variables could be clinically feasible targets for biofeedback to improve gait after ACLR. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis is a common, progressive, and chronic disease that affects approximately 13% of the population over the age of 60. Osteoarthritis causes progressive disability and changes in gait parameters, decreased function and quality of life of patients by causing malalignment of the knee in the frontal plane following destruction of articular cartilage. Braces as a mechanical intervention are a successful treatment for osteoarthritis knee and its associated malalignment. Using a three-point pressure mechanism, braces create a natural alignment in the knee by straps attached to the thigh and shank shells, which reduce the medial knee load and correct the varus alignment. This distributes the force properly while walking. However, applying a constant force on three pressure points of the leg, thigh and affected knee joint reduces the adduction angle of the knee in all phases of gait cycle, while the correction of the adduction angle of the knee in patients is essential only in phases between 30% to 60% of the stance phase, when the knee deviation reaches its peak. The aim of this study is to design and fabricate a brace joint with a new intermittent correction mechanism for patients with osteoarthritis medial compartment knee and to investigate its effect on a patient's gait parameters. Materials & Methods: The new joint design of the knee brace was based on the conversion of the knee extension movement at the end of the swing on the sagittal plane to the abduction movement on the frontal plate by stretching the converter piece. Participant gait was assessed in two ways with and without braces. Kinematic variables including knee joint angles in the sagittal and frontal planes and spatiotemporal variables of patient gait were measured and recorded. Results: The results of the new brace joint function on the knee showed that the angle of flexion of the knee in the swing phase increased from 44.72° to 46.19° when using brace. Also, knee adduction angle in the stance phase decreased from 4.25° to 2.3° and patient's walking speed while wearing the brace increased from 0.88 m/s to 0.93 m/s. On the other hand, step length increased from 1.125 m to 1.451 m when using brace and the percentage of stance phase decreased from 63.53 to 62.68 when using brace. Conclusion: In this one-sample study, a knee brace with a new joint was able to help correct the direction of knee joint in the frontal and sagittal plane and affect the patient's gait parameters. It seems that if the same results are obtained in a large-scale clinical study, this brace could be a suitable replacement for invasive methods and inappropriate orthoses. [ABSTRACT FROM AUTHOR]

Backgrounds: As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understanding of the genetic etiology of OA.Methods: Six participants (3 OA and 3 controls) were recruited and serum samples were assayed through RNA sequencing (RNA-seq). And, RNA-seq dataset was analysed to identify genes, pathways and regulatory networks dysregulated in OA. The overlapped differentially expressed microRNAs (DEMs) were further screened in combination with the microarray dataset GSE143514. The expression levels of candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) based on the GEO dataset (GSE114007).Results: Serum samples were sequenced interrogating 382 miRNAs. After screening of independent samples and GEO database, the two comparison datasets shared 19 overlapped candidate micRNAs. Of these, 9 up-regulated DEMs and 10 down-regulated DEMs were detected, respectively. There were 236 target genes for up-regulated DEMs and 400 target genes for those down-regulated DEMs. For up-regulated DEMs, the top 10 hub genes were KRAS, NRAS, CDC42, GDNF, SOS1, PIK3R3, GSK3B, IRS2, GNG12, and PRKCA; for down-regulated DEMs, the top 10 hub genes were NR3C1, PPARGC1A, SUMO1, MEF2C, FOXO3, PPP1CB, MAP2K1, RARA, RHOC, CDC23, and CREB3L2. Mir-584-5p-KRAS, mir-183-5p-NRAS, mir-4435-PIK3R3, and mir-4435-SOS1 were identified as four potential regulatory pathways by integrated analysis.Conclusions: We have integrated differential expression data to reveal putative genes and detected four potential miRNA-target gene pathways through bioinformatics analysis that represent new mediators of abnormal gene expression and promising therapeutic targets in OA. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of foot progression angle on the reduction in knee adduction moment caused by a lateral wedged insole during walking. Twenty healthy, young volunteers walked 10 m at their comfortable velocity wearing a lateral wedged insole or control flat insole in 3 foot progression angle conditions: natural, toe-out, and toe-in. A 3-dimensional rigid link model was used to calculate the external knee adduction moment, the moment arm of ground reaction force to knee joint center, and the reduction ratio of knee adduction moment and moment arm. The result indicated that the toe-out condition and lateral wedged insole decreased the knee adduction moment in the whole stance phase. The reduction ratio of the knee adduction moment and the moment arm exhibited a close relationship. Lateral wedged insoles decreased the knee adduction moment in various foot progression angle conditions due to decrease of the moment arm of the ground reaction force. Moreover, the knee adduction moment during the toe-out gait with lateral wedged insole was the smallest due to the synergistic effect of the lateral wedged insole and foot progression angle. Lateral wedged insoles may be a valid intervention for patients with knee osteoarthritis regardless of the foot progression angle. [ABSTRACT FROM AUTHOR]

Intra‐articular injection of mesenchymal stem cells has shown benefit for the treatment of osteoarthritis (OA). However, mesenchymal stem/stromal cells at the origin of these clinical results are heterogenous cell populations with limited cellular characterization. Here, two transgenic reporter mice were used to examine the differential effects of two precisely defined perivascular cell populations (Pdgfrα+ and Pdgfrβ+ cells) from white adipose tissue for alleviation of OA. Perivascular mesenchymal cells were isolated from transgenic Pdgfrα‐and Pdgfrβ‐CreERT2 reporter animals and delivered as a one‐time intra‐articular dose to C57BL/6J mice after destabilization of the medial meniscus (DMM). Both Pdgfrα+ and Pdgfrβ+ cell preparations improved metrics of cartilage degradation and reduced markers of chondrocyte hypertrophy. While some similarities in cell distribution were identified within the synovial and perivascular spaces, injected Pdgfrα+ cells remained in the superficial layers of articular cartilage, while Pdgfrβ+ cells were more widely dispersed. Pdgfrβ+ cell therapy prevented subchondral sclerosis induced by DMM, while Pdgfrα+ cell therapy had no effect. In summary, while both cell therapies showed beneficial effects in the DMM model, important differences in cell incorporation, persistence, and subchondral sclerosis were identified. [ABSTRACT FROM AUTHOR]

BACKGROUND: Total knee arthroplasty is an effective method for the treatment of end-stage knee osteoarthritis. The key to total knee arthroplasty is to restore the accurate lower limb alignment and good flexion and extension space balance. Gap balance technique and measurement osteotomy technique are two classical osteotomy methods, which methods to choose is still controversial. OBJECTIVE: To compare radiographical manifestations of gap balance technique and measurement osteotomy technique in total knee arthroplasty patients, and analyze application effect of gap balance technique in total knee arthroplasty patients. METHODS: Clinical data of 118 patients with total knee arthroplasty were retrospectively analyzed, including 42 males and 76 females, aged 53-72 years old. According to intraoperative osteotomy methods, they were divided into gap balance group (61 cases) and measurement osteotomy group (57 cases). In 12-month follow-up, X-ray films were taken to measure the coronal hip-knee-ankle angle, lower line force angle and femoral flexion angle. Visual analogue scale score and American knee society knee score were used to evaluate the pain degree and knee function. This study was approved by the Ethics Committee of Guiyang Fourth People’s Hospital. RESULTS AND CONCLUSION: (1) The gap balance group had local infection in three cases. The measurement osteotomy group had local infection in four cases, rejection in one case, and immune reaction in one case. There was no significant difference in complications between the two groups (4.92%, 10.53%, P > 0.05). (2) In 12-month follow-up, knee flexion 90° stress angle of medial and lateral tibiofemoral joint was lower in the gap balance group than that in the measurement osteotomy group (P < 0.001). Coronal hip-knee-ankle angle and lower limb alignment were smaller in the gap balance group than those in the measurement osteotomy group (P < 0.001). Maximum femoral flexion angle was larger in the gap balance group than that in the measurement osteotomy group (P < 0.001). (3) In 12-month follow-up, visual analogue scale scores were lower in the gap balance group than those in the measurement osteotomy group (P < 0.001). American knee society knee score was higher in the gap balance group than that in the measurement osteotomy group (P < 0.01). (4) Results showed that gap balance technology help to maintain a good lower limb alignment and flexion extension gap space, relieve the pain and improve the knee function during total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Epigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations. Genome‐wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip. Several significantly differentially methylated positions (DMPs) and regions were found between tissue types. Substantial OA‐related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA‐related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA‐related methylation patterns in primates. Overall, these findings reinforce the current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This study further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify osteoarthritis (OA) related genes based on microarray data in synovium with a more robust integrative analysis method. Methods: Four series GSE55457, GSE12021, GSE55235, and GSE55584 (36 OA and 29 normal samples) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) of GSE55457, GSE12021, and GSE55235 were identified using the LIMMA package. Overlapping DEGs from the intersection of the three series were detected. Simultaneously, samples in the four series were pooled to identify DEGs with integrated analysis using the Sva package. Results: In total, 74 overlapping DEGs and 242 DEGs by integrating four series were detected. Based on them, 70 common DEGs were used to construct a protein-protein interaction (PPI) network, involving 61 nodes and 206 edges. Also, three gene modules and five hub genes, named JUN, IL6, VEGFA, MYC, and EGR1, were identified. Conclusions: Seventy DEGs were finally identified with a more robust integrative analysis method. JUN, IL6, VEGFA, MYC, and EGR1 were identified as hub genes in the development of OA. Key Points • 76 overlapping DEGs were detected from the intersection of DEGs in GSE55457, GSE12021, and GSE55235. • 242 DEGs were identified by integrating four series using Sva package. • 72 common DEGs were finally identified based on the overlapping DEGs and the integrated DEGs. • JUN, IL6, VEGFA, MYC, and EGR1 were identified as hub genes in the development of OA. [ABSTRACT FROM AUTHOR]

Background: Radiographic factors estimate the state of the static knee joint, and it is questionable how well these parameters reflect the dynamic knee condition. The external knee adduction moment (KAM) during gait is known to be a kinetic variable contributing to osteoarthritis progression. This study aims to investigate the effects of static radiographic parameters on the dynamic KAM during gait.Methods: Overall, 123 patients (mean age, 65.7 years; standard deviation, 8.1 years; 34 men and 89 women) were included. Seven radiographic parameters including the mechanical tibiofemoral angle (mTFA), Kellgren-Lawrence grade, and ankle joint line orientation (AJLO) were measured on radiographs, and the maximum KAM and KAM-time integral in the stance phase were obtained using three-dimensional gait analysis. The correlation and multiple regression analyses were performed for identifying significant radiographic measurements associated with the KAM.Results: Most of the radiographic measurements correlated with the maximum KAM and KAM-time integral. As a result of multiple regression analysis, the mTFA (p < 0.001) and AJLO (p = 0.003) were identified as significant factors associated with the KAM-time integral (R2 = 0.450); the mTFA (p < 0.001) and AJLO (p = 0.003) were identified as a significant factor associated with the maximum KAM (R2 = 0.352) in multiple regression analysis. The discriminant validity of KAM was highest at varus 5.7 degree of the mTFA and 7.5 degree of the AJLO.Significance: The mTFA and AJLO were significantly associated with the KAM. However, to be used as a surgical indication for corrective osteotomy, a longitudinal study is needed to validate whether the mTFA and AJLO values directly cause osteoarthritis progression as we have suggested.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Background: Patients with hip osteoarthritis (OA) exhibit an increased step width (SW) during walking before and up to 2 years after total hip arthroplasty. Wider SW is associated with a reduction in the external knee adduction moment (KAM), but there is a lack of research regarding the effect of SW on the hip adduction moment (HAM).Research Question: Is a wider SW an effective compensatory mechanism to reduce the hip joint loading? We hypothesized that (1) an increased SW reduces, (2) a decreased SW increases the KAM/HAM, and (3) secondary kinematic gait changes have an effect on the KAM/HAM.Methods: Twenty healthy individuals (24.0 ± 2.5 years of age) underwent instrumented gait analyses with 4 different subject-specific SW modifications (habitual, halved, double, and triple SW). The resulting external KAMs and HAMs were compared using statistical parametric mapping (SPM).Results: Post hoc testing demonstrated significantly lower HAM for both the double (p < 0.001, 15-31 % and 61-98 % of the stance phase) and the triple SW (p < 0.001, 1-36 % and 58-98 %) compared to the habitual SW. The extent of the reduction at the first and second peak was comparable for HAM (15-25 % reduction) and less pronounced at the first peak of KAM (9-11 % reduction) compared to the second peak of KAM (19-28 % reduction). In contrast, halving the SW did not lead to a significant change in KAM or HAM compared to the habitual SW (p > 0.009).Significance: An increase in SW is an effective and simple gait mechanism to reduce the frontal plane knee and hip joint moments. However, hypothesis 2 could not be confirmed, as halving the SW did not cause a significant change in KAM or HAM. Given the results of the present study, gait retraining with regard to an increased SW may be an adequate, noninvasive option for the treatment of patients with hip OA. [ABSTRACT FROM AUTHOR]

Aim: Previous studies have provided evidence linking the DPEP1 gene to the risk of osteoarthritis (OA) in Europeans. In this study, we aimed to examine the relationship between DPEP1 gene and the susceptibility and clinical severity of OA in a Chinese Han population. Methods: This study comprised two independent samples. For the discovery stage, 1022 patients with knee OA and 1864 controls were recruited. Fourteen tag single nucleotide polymorphisms (SNPs) covering the DPEP1 gene were selected and genotyped. Associated SNPs in the discovery data set were subsequently genotyped in the replication data set consisting of 826 hip OA cases and 1662 controls. Both genotypic and allelic genetic associations were tested. The relationship of significant SNPs to the expression of DPEP1 and its neighboring genes was examined using the GTEx database. Results: A nonsynonymous SNP, rs1126464, was determined to be associated with the disease status of OA in both the discovery and replication stages (odds ratio [OR] 0.75, 95% confidence interval [95% CI] 0.68‐0.82, P = 7.16 × 10−11). This SNP was further characterized as being significantly related to a higher Kellgren‐Lawrence grade in OA patients (OR 0.64, 95% CI 0.55‐0.74, P = 2.53 × 10−9). According to the GTEx data, SNP rs1126464 was significantly related to the gene expression of 15 genes in multiple types of human tissues. Conclusion: We reported a common DNA variant in the DPEP1 gene that contributes to the risk of OA, providing additional evidence that the DPEP1 gene plays a significant role in the pathological mechanisms of OA. [ABSTRACT FROM AUTHOR]

Background: Lateral wedge insoles adjusted by biomechanical analysis may improve the condition of patients with medial knee osteoarthritis. Design: This is a prospective, randomized, controlled, single-blind clinical trial. Setting: The study was conducted in a biomechanics laboratory. Subjects: A total of 38 patients with medial knee osteoarthritis were allocated to either an experimental group (lateral wedge insoles) or a control group (neutral insoles). Interventions: Experimental group (n = 20) received an adjusted lateral wedge insole of 2, 4, 6, 8, or 10 degrees, after previous biomechanical analysis. Control group (n = 18) received a neutral insole (0 degrees). All patients used the insoles for 12 weeks. Main measures: Visual analogue scale, Knee Injury and Osteoarthritis Outcome Score questionnaire, biomechanical parameters: first and second peak of the external knee adduction moment and knee adduction angular impulse, and physical performance tests: 30-second sit-to-stand test, the 40-m fast-paced walk test, and the 12-step stair-climb test. Results: After 12 weeks, between-group differences did not differ significantly for pain intensity (−12.5 mm, (95% CI −29.4–4.4)), biomechanical parameters (p = 0.05), Knee Injury and Osteoarthritis Outcome Score, and physical performance tests, except on the Knee Injury and Osteoarthritis Outcome Score subscale other symptoms (p = 0.002; 13.8 points, (95% CI 5.6–22.0)). Conclusion: Tailored wedge insoles were no more effective at improving biomechanical or clinically meaningful outcomes than neutral insoles, except on symptoms. More participants from the experimental group reported they felt some improvement. However, these effects were minimal and without clinical significance. [ABSTRACT FROM AUTHOR]

Purpose: To determine the duration of symptom relief following repeated administration of hyaluronic acid injections for osteoarthritis. Patients and Methods: This was a 6-year observational study with 623 consecutive patients who had received hyaluronic acid injections. The primary outcome measure was the mean time between injections measured in days. Classical one-sample 2-sided t-tests, one-way analysis of variances and post-hoc analyses were performed to determine if there were statistically significant differences between age, gender, radiographic severity and the type of joints injected. All patients were invited to complete an online post-treatment experience and satisfaction survey. Results: The analysis included 727 joints (mean Kellgren-Lawrence grade, 2.9 ± 0.8 (range 2– 4)) in 623 patients (297 (47.7%) male; mean age at first injection, 57.8 ± 12.7 years (range 21.2– 92.1)). Patients ranged from having 1– 8 injections per joint. The mean time between injections in days was 466.8 ± 321.7 (2nd injection, 157 joints), 400.5 ± 164.7 (3rd injection, 58 joints), 378.2 ± 223.1 (4th injection, 27 joints), 405.3 ± 216.3 (5th injection, 7 joints), 268.4 ± 104.4 (6th injection, 5 joints), 289.8 ± 99.4 (7th injection, 4 joints), and 272.5 ± 33.2 (8th injection, 2 joints). Patients with grades 2 and 3 compared to grade 4 osteoarthritis experienced a longer time between injections (F (2, 154) = 3.53, p = 0.0316). No statistically significant differences were observed between age, gender, or joint groups. The survey included 233 participants (109 (46.8% male)). A total of 144 respondents (64.9%) recommended hyaluronic acid injections for osteoarthritis. Conclusion: Pain relief from hyaluronic acid injections was sustained for on average 466.8 days post initial treatment. Patients who received subsequent 3rd, 4th, and 5th injections also experienced extended duration of benefit. Patients with grades 2 or 3 osteoarthritis are more likely to experience a longer duration of relief. [ABSTRACT FROM AUTHOR]

The systematic review aimed to analyze the effects of resistance training in knee osteoarthritis (OA) rehabilitation from a biomechanical perspective. A meta-analysis was performed to determine the potential benefits of resistance training on patients with knee OA. Relevant studies based on the inclusion and exclusion criteria were selected from CENTRAL, PubMed, Scopus, and Web of Science databases inception to August 2020. Outcome measures included gait velocity and knee adduction moment (KAM). The mean differences of the data with a 95% confidence interval were analyzed using STATA 15.1 software The search identified eight studies that satisfied all the inclusion criteria, in which 164 patients were involved in gait velocity studies and another 122 patients were part of KAM studies. Analysis of the pooled data showed that resistance training significantly improved the gait velocity in patients with knee OA (p < 0.01, z = 2.73), ES (95% CI) = 0.03 (0.01, 0.06) m/s. However, resistance training had no significant effect on improving KAM in patients with knee OA (p = 0.98, z = 0.03), ES (95% CI) = 0.00 (− 0.16, 0.16) percentage of body weight × height (%BW × Ht). Therefore, resistance training may enhance gait velocity but not KAM in knee OA patients. The protocol was registered at PROSPERO (registration number: CRD42020204897). [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common cause of disability, especially among the elderly. With an ageing and increasingly obese population, OA will become more prevalent. Obesity and metabolic syndrome are risk factors for OA and have been implicated in its pathogenesis. The gut microbiome may shed light on this possible common pathogenesis. Recent animal and human studies have gained important insights into the relationship between OA, obesity, and the gut microbiome. Animal studies have demonstrated links between obesity and increased severity of OA and altered gut microbial DNA profile. Use of prebiotics and probiotics in animal trials provides proof‐of‐concept that interventional options to the gut microbiome can modulate the progression of OA favorably. Current evidence in human studies is limited. Shifts in gut microbial profile and reduced gut microbial diversity have been associated with people with OA, as well as blood and synovial fluid lipopolysaccharide endotoxemia. Linkages between microbiome dysbiosis and host responses may help in the understanding of OA pathogenesis and the discovery of therapeutic targets. This narrative review provides a summary of up‐to‐date animal and human studies on the gut microbiome and its link with OA. [ABSTRACT FROM AUTHOR]

(1) Background: The femoroacetabular impingement (FAI) type cam leads to a conflict between the acetabular rim and a bony thickening of the femoral neck junction. While maximal excursions in flexion, adduction and internal rotation provoke pain, the aim of this study was to analyze if a cam morphology shows an impact on gait pattern. (2) Methods: Fifty-five patients with end-stage hip osteoarthritis performed gait analysis before hip replacement as well as three, six and 12 months postoperatively. Thirty-three (60%) of them presented an FAI type cam. An ANOVA was used to compare the hip angles in sagittal, frontal and transversal planes between patients with a FAI type cam (group "+cam") and without (group "−cam"). (3) Results: Before surgery the patients of the +cam-group showed a tendency towards a reduced flexion and internal rotation at the heel strike (p > 0.05). Over time, the differences were adjusted by total hip arthroplasty. (4) Conclusions: We did not find any differences in the gait analysis of patients with a FAI type cam compared to patients without. [ABSTRACT FROM AUTHOR]