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Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine‐mediated pathological communication between the synovium and cartilage. Cartilage‐specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network‐based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M (OSM), as a driver of the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of OSM recapitulated an "inflammatory" phenotype of knee osteoarthritis and highlighted high‐value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation‐driven osteoarthritis phenotype. [ABSTRACT FROM AUTHOR]

Early detection of knee osteoarthritis (KOA) can improve treatment outcomes and prevent its progression. The aim of this systematic review was to identify the functional changes in early KOA. Electronic journal databases and platforms, including PubMed, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, and Scopus were searched. The inclusion criteria were as follows: (1) studies comparing patients with early KOA with an age-matched control group and (2) studies with objectively measured functional changes as outcomes. Studies that included individuals with Kellgren and Lawrence (K/L) grades > 2- were excluded. A random-effects model was constructed to calculate pooled standardized mean differences (SMDs). A total of nine articles were included in this systematic review. Seven studies used classification criteria to define early KOA, including knee pain; a K/L grade of 0, 1, or 2- (osteophytes only) for the medial compartment; and the presence of two out of four MRI criteria. The remaining two studies included K/L grade 1 confirmed by radiography. Early KOA participants had a significantly longer timed up-and-go test (TUG) time (pooled SMD: 0.57; 95% confidence interval: 0.15, 0.98). The two groups had similar knee extension muscle strength at 90° knee flexion. The quality of evidence for each measured outcome was "very low." In this review, longer TUG was identified as a functional manifestation of early KOA. Further studies involving functional assessments are needed to develop a screening method to detect early KOA. Key Points • There is a need for diagnostic criteria that include functional changes in patients with early knee osteoarthritis, since radiographic facilities are not available everywhere. • In this review, a long timed up-and-go test time was identified as a functional manifestation of early knee osteoarthritis. • If the findings of this study can be replicated, measurement of TUG may allow for earlier detection of knee osteoarthritis outside the hospital and in routine clinical practice without the use of MRI or X-rays. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a leading cause of knee pain and disability due to irreversible cartilage degeneration. Previous studies have not identified modifiable risk factors for KOA. In this preliminary cross-sectional study, we aimed to test the following hypotheses: individuals with severe KOA would have a significantly lower quadriceps rate of force development (RFD) than individuals with early KOA, and the decrease in quadriceps RFD would be greater than the decrease in maximum quadriceps strength in individuals with severe KOA. The maximum isometric strength of the quadriceps was assessed in individuals with mild (Kellgren and Lawrence [K&L] grade 1–2) and severe KOA (K&L grade 3–4) using a handheld dynamometer. The RFD was analyzed at 200 ms from torque onset and normalized to the body mass and maximum voluntary isometric contraction torque. To test whether the quadriceps RFD was lowered and whether the lower in the quadriceps RFD was greater than the lower in maximum quadriceps strength in individuals with severe knee OA, the Mann–Whitney U-test and analysis of covariance were performed, respectively. The effect size (ES) based on Hedges' g with a 95% confidence interval (CI) was calculated for the quadriceps RFD and maximum quadriceps strength. Sixty-six participants were analyzed. Individuals with severe KOA displayed significantly lower quadriceps RFD (p = 0.009), the lower being greater than the lower in maximum quadriceps strength (between-group difference, ES: 0.88, -1.07 vs. 0.06, -0.22). Our results suggest that a decreased quadriceps RFD is a modifiable risk factor for progressive KOA. Our finding could help in the early detection and prevention of severe KOA. [ABSTRACT FROM AUTHOR]

Introduction/objectives: This study aimed to investigate the association between hip abductor muscle strength and knee pain in patients with early-stage knee osteoarthritis (OA) while ascending and descending stairs. Method: This cross-sectional study included individuals with early-stage knee OA (Kellgren/Lawrence grades 1 or 2). Knee pain while ascending and descending stairs was evaluated using a knee OA-related health domain measure (Japanese Knee Osteoarthritis Measure). Knee extension and hip abductor muscle strength were also evaluated. The association between hip abductor muscle strength and knee pain while ascending and descending stairs was evaluated using multiple regression analysis. Results: A total of 157 participants were included in the final analysis. After the adjustment for age, sex, and knee extension strength, those with knee pain while descending stairs showed significantly decreased hip abductor muscle strength (β, − 0.09; 95% confidence interval [CI], − 0.19 to − 0.003). In contrast, after the adjustment for age, sex, and knee extension muscle strength, those with knee pain while ascending stairs did not have significantly decreased hip abductor muscle strength (β, − 0.06; 95% CI, − 0.15 to 0.02). Conclusions: Patients with early-stage knee OA and knee pain while descending stairs had significantly reduced hip abductor muscle strength. [ABSTRACT FROM AUTHOR]

Abstract Clarifying proximal gait adaptations as a strategy to reduce knee joint loading and pain for individuals with knee osteoarthritis (OA) contributes to understanding the pathogenesis of multi-articular OA changes and musculoskeletal pain in other joints. We aimed to determine whether biomechanical alterations in knee OA patients during level walking is increased upper trunk lean in the frontal and sagittal planes, and subsequent alteration in external hip adduction moment (EHAM) and external hip flexion moment (EHFM). A literature search was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL through May 2018. Where possible, data were combined into a meta-analysis; pooled standardized mean differences (SMD) of between knee OA patients and healthy adults were calculated using a random-effect model. In total, 32 articles (2037 participants, mean age, 63.0 years) met inclusion criteria. Individuals with knee OA had significantly increased lateral trunk lean toward the ipsilateral limb (pooled SMD: 1.18; 95% CI: 0.59, 1.77) along with significantly decreased EHAM. These subjects also displayed a non-significantly increased trunk/pelvic flexion angle and EHFM. The GRADE approach judged all measures as " very low." These results may indicate that biomechanical alterations accompanying knee OA are associated with increased lateral trunk lean and ensuing alterations in EHAM. Biomechanical alterations in the sagittal plane were not evident. Biomechanical adaptations might have negative sequelae, such as secondary hip abductor muscle weakness and low back pain. Thus, investigations of negative sequelae due to proximal gait adaptations are warranted. [ABSTRACT FROM AUTHOR]

Background: Stair climbing is the task first affected in patients with knee osteoarthritis (OA); therefore, the precise measurement of time required to climb stairs is important to identify mobility limitations, particularly in the early phase of knee OA.Research Question: This study aimed to examine the test-retest reliability, measurement error, and concurrent validity of the stopwatch-based stair-climb test (SCT) in adults with pre-radiographic to mild knee OA.Methods: Fifty-nine participants (mean age, 59.1 [range, 50-69] years; 72.9% female) with Kellgren and Lawrence grade ≤2 disease underwent an 11-step SCT (11-SCT) in accordance with the Osteoarthritis Research Society International recommended method while wearing pressure sensor-mounted standard shoes that is used as a gold standard procedure. Test-retest reliability, measurement errors, and the concurrent validity of the stopwatch-based 11-SCT were evaluated.Results: The test-retest reliability of the stopwatch-based 11-SCT was excellent (intra-class correlation coefficient1,1 [ICC1,1], 0.952; 95% confidence interval [CI], 0.560 to 0.985; p <  0.001) and the minimal detectable change95 was 0.102 s. Concurrent validity was excellent (ICC2,1: 0.957; 95% CI: 0.661 to 0.986; p <  0.001).Significance: The stopwatch-based 11-SCT had high test-retest reliability and high concurrent validity, which justify its clinical use for identifying mobility limitations in individuals with pre-radiographic to mild knee OA. A difference of 0.2 s in the stopwatch-based 11-SCT time would be considered a true difference beyond a 95% measurement error. [ABSTRACT FROM AUTHOR]

To compare the efficacy and adherence rates of two parallel home exercise therapy programs—multiple exercise (training and stretching the knee and hip muscles) and control (training the quadriceps muscles)—on knee pain, physical function, and knee extension strength in community-dwelling elderly individuals with pre-radiographic knee osteoarthritis (OA). One hundred patients with medial knee pain were randomly allocated to one of two 4-week home exercise programs. Individuals with a Kellgren/Lawrence (K/L) grade 0 or 1 OA (pre-radiographic knee OA) in the medial compartment were enrolled. Primary outcomes were knee pain (visual analog scale), self-reported physical function (Japanese Knee Osteoarthritis Measure [JKOM]), and isometric maximum muscle strength of the knee extensor measured using a hand-held dynamometer. A total of 52 patients (28 [53.8%] in the multiple exercise group, 24 [46.2%] in the control group) completed the trial. The JKOM activities of daily living and general health conditions outcomes improved significantly in the multiple exercise group compared to the control group (JKOM activities of daily living, beta = − 0.76; 95% confidence interval [CI], − 1.39 to − 0.13; p = 0.01; JKOM general health conditions, beta = − 0.25; 95% CI, − 0.48 to − 0.01; p = 0.03). The home exercise compliance rates of the multiple exercise and control groups were 96.6 and 100%, respectively. When targeting pre-radiographic knee OA in community-dwelling elderly, it is important to implement home exercise programs that aim to improve muscle strength and joint flexibility rather than knee extension muscle power only. [ABSTRACT FROM AUTHOR]

Background: Stair climbing was suggested to be the first affected task in individuals with knee osteoarthritis (OA).Research Question: This review aimed to identify consistent kinematic, kinetic, and spatiotemporal alterations of stair climbing exhibited by individuals with knee OA.Methods: A literature search published until September 2017 was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL. Reviewer extracted data in accordance with the Cochrane Handbook. Where possible, data were combined into a meta-analysis; the pooled standardized mean differences between individuals with knee OA and healthy adults were calculated using the random-effect model.Results: In total, 585 potentially relevant articles were selected, of which 12 (695 participants, mean age: 58.4 years) met the inclusion criteria. Meta-analysis revealed that kinematic and kinetic alterations during stair climbing associated with knee OA were lower external knee flexion moment in conjunction with a larger trunk/hip flexion angles and smaller knee flexion/ankle dorsiflexion angles. Individuals with knee OA showed a delayed quadriceps activation during stair ascent. A lack of evidence was detected for alterations in external knee adduction moment during stair climbing. Effect estimate in each meta-analysis was judged "very low" on the GRADE approach.Significance: No strong conclusion can be drawn because of the low quality of evidence; however, individuals with knee OA may exhibit altered kinematics and kinetics changes in sagittal plane during stair climbing, and have delayed quadriceps muscle activity. Further studies with adequate adjustment for confounders are warranted to facilitate clinical hallmarks of the knee OA, particularly in early stages of the disease. [ABSTRACT FROM AUTHOR]

Objective: Despite the increased use of platelet-rich plasma in the treatment of osteoarthritis, whether and how age of the platelet-rich plasma donor affects therapeutic efficacy is unclear. Design: In vitro, male osteoarthritic human chondrocytes were treated with platelet-rich plasma from young (18–35 yrs) or old (≥65 yrs) donors, and the chondrogenic profile was evaluated using immunofluorescent staining for two markers of chondrogenicity, type II collagen and SOX-9. In vivo, we used a within-subjects design to compare Osteoarthritis Research Society International scores in aged mouse knee joints injected with platelet-rich plasma from young or old individuals. Results: In vitro experiments revealed that platelet-rich plasma from young donors induced a more youthful chondrocyte phenotype, as evidenced by increased type II collagen (P = 0.033) and SOX-9 expression (P = 0.022). This benefit, however, was significantly blunted when cells were cultured with platelet-rich plasma from aged donors. Accordingly, in vivo studies revealed that animals treated with platelet-rich plasma from young donors displayed a significantly improved cartilage integrity when compared with knees injected with platelet-rich plasma from aged donors (P = 0.019). Conclusions: Injection of platelet-rich plasma from a young individual induced a regenerative effect in aged cells and mice, whereas platelet-rich plasma from aged individuals showed no improvement in chondrocyte health or cartilage integrity. [ABSTRACT FROM AUTHOR]

Laser range sensor-based timed up and go (laser-TUG) test can evaluate performance in TUG subtasks (sit-to-walk [STW], walking a short distance, and turning). This study aimed to test the hypothesis that weaker hip abductor muscle strength is more significantly associated with slowed turning speed than with the other TUG subtasks (STW and straight walking) after controlling for quadriceps muscle strength in patients with knee osteoarthritis (OA). Community-dwelling participants with knee OA (Kellgren and Lawrence [K&L] grade ≥ 1; mean age, 68.6 years; 70.3% women) underwent laser-TUG. Spatiotemporal gait parameters in TUG and the TUG subtasks were evaluated as outcome measures. The isometric muscle strength of the hip abductor and quadriceps was measured using a hand-held dynamometer. Multiple linear regression analysis was performed to examine the relationship between muscle strength as an independent variable and spatiotemporal parameters as dependent variables. The relative importance of hip abductor muscle strength was determined using the percentages of unique variance. Participants with weaker hip abductor muscle strength demonstrated 0.094 m/s slower turning speed after adjustment for covariates including quadriceps muscle strength. The unique variance explained by hip abductor muscle strength in turning speed was 2.1%. However, no significant relationships were confirmed between weak hip abductor muscle strength and the time to perform TUG and the straight walking (forward and return) phase. These findings indicate that turning motion may be more sensitive to aggravated hip abductor muscle weakness and may show better response to hip muscle strengthening exercises. Longitudinal studies are warranted to elucidate this issue. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) progression is associated with an increase in peak external knee flexion torque (EKFT) during gait. However, the difference in the peak EKFT between individuals with knee OA and age-matched subjects was unclear. Therefore, to understand the kinematics, kinetics, and electromyogram characteristics in individuals with knee OA, we conducted a systematic review and meta-analysis of sagittal plane-dominant sit-to-stand (STS) motion. PubMed, PEDro, CINAHL, and Cochrane CENTRAL were used. Fourteen articles (knee-OA group: n = 323, mean age = 65.0 years, mean weight = 79.2 kg; control group: n = 224, mean age = 64.4 years, mean weight = 70.4 kg) were included, and the pooled standardized mean differences (SMDs) were calculated using a random-effects model. Meta-analysis showed that individuals with knee OA present significantly lower peak EKFT (pooled SMD: −1.62; 95% confidence interval [CI]: −2.36 to −0.88), significantly large trunk flexion angle (pooled SMD: 1.04; 95% CI: 0.69 to 1.39), and no significantly lower peak external knee adduction torque despite the significantly larger lateral-lean angle to the less affected side (pooled SMD: 1.04; 95% CI: 0.69 to 1.39). The quality of evidence for all outcomes was very low. The descriptive synthesis indicates that STS motion in individuals with knee OA might be an unsuitable motion strategy for knee muscle activity, force utilization from multiple joints to the knee joint, and their influence on knee joint cartilage, despite their lower peak EKFT. This information can help to better understand movement strategies and to optimize treatment approaches for individuals with knee OA. [ABSTRACT FROM AUTHOR]