This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria (n = 2385 patients; mean age: 36.0–74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: −1.45, 95% confidence interval [CI]: −1.94, −0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: −1.99; 95% CI: −3.51, −0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: −0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2–60%; however, no severe adverse events occurred. The evidence for these outcomes was “very low” to “low” according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA.

BackgroundDepressive symptoms are a major comorbidity in older adults with knee osteoarthritis (OA). However, the type of activity-induced knee pain associated with depression has not been examined. Furthermore, there is conflicting evidence regarding the association between depression and performance-based physical function. This study aimed to examine (i) the association between depressive symptoms and knee pain intensity, particularly task-specific knee pain during daily living, and (ii) the association between depressive symptoms and performance-based physical function, while considering other potential risk factors, including bilateral knee pain and ambulatory physical activity.MethodsPatients in orthopaedic clinics (n = 95; age, 61–91 years; 67.4% female) who were diagnosed with radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥ 1) underwent evaluation of psychological health using the Geriatric Depression Scale (GDS). Knee pain and physical function were assessed using the Japanese Knee Osteoarthritis Measure (JKOM), 10-m walk, timed up and go (TUG), and five-repetition chair stand tests.ResultsOrdinal logistic regression analysis showed that depression, defined as a GDS score ≥ 5 points, was significantly associated with a worse score on the JKOM pain-subcategory and a higher level of task-specific knee pain intensity during daily living, after being adjusted for age, sex, body mass index (BMI), K/L grade, and ambulatory physical activity. Furthermore, depression was significantly associated with a slower gait velocity and a longer TUG time, after adjusting for age, sex, BMI, K/L grade, presence of bilateral knee pain, and ambulatory physical activity.ConclusionsThese findings indicate that depression may be associated with increased knee pain intensity during daily living in a non-task-specific manner and is associated with functional limitation in patients with knee OA, even after controlling for covariates, including bilateral knee pain and ambulatory physical activity.Electronic supplementary materialThe online version of this article (10.1186/s40359-018-0234-3) contains supplementary material, which is available to authorized users.

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Objective: Individuals with stroke frequently experience mobility deficits and limited community reintegration. This study aimed to investigate life-space mobility and relevant factors in community-living individuals with stroke. Methods: This was a cross-sectional study of 46 community-dwelling individuals with chronic stroke in Japan (mean age 72.7 ± 7.4 years; mean time post-stroke 63.6 ± 43.3 months; 26 men/20 women). We measured life-space mobility using a Japanese translation of the Life-Space Assessment. The following factors that might affect life-space mobility were assessed: the ability to perform activities of daily living, physical performance, fear of falling, and cognitive function. Results: A total of 41 participants (89.1%) had restricted life-space mobility (Life-Space Assessment score <60 points). A multiple linear regression analysis showed that limitations in activities of daily living, walking speed, and Falls Efficacy Scale-International scores were independently related to Life-Space Assessment scores. This model explained 51.3% of the variance in Life-Space Assessment scores. Conclusions: Most individuals with stroke had restricted life-space mobility. Life-space mobility was associated with the ability to perform activities of daily living, walking speed, and fear of falling. These findings could contribute to the development of rehabilitation interventions for regaining life-space mobility in individuals with stroke.

This cross-sectional study examined the relationship of flat feet with knee pain, disability, and physical performance in patients with knee osteoarthritis (OA). Orthopedic clinic participants (n = 95; age 61-91 years; 68.4% women) with Kellgren-Lawrence (K/L) grade ≥1 in the medial compartment underwent evaluation of navicular height and foot length for flat feet. Knee pain intensity, disability, and physical performance were evaluated using the Japanese Knee Osteoarthritis Measure, 10-m walk, timed up and go, and five-repetition chair stand tests. Of the 95 enrolled patients, 24 (25.3%) had bilateral flat feet, and significantly higher knee pain compared to patients with no flat feet (11.3 ± 8.23 points vs. 6.58 ± 6.37 points; p = 0.043). A ordinal logistic regression analysis showed that bilateral flat feet were significantly associated with increased knee pain (proportional odds ratio: 5.48, 95% confidence interval: 1.96, 15.3; p = 0.001) compared with no flat feet, adjusted for age, sex, body mass index, and tibiofemoral joint K/L grade, which is consistent across various different cutoffs of the definition of flat feet. Physical performance was similar between patients with and without bilateral flat feet. The presence of unilateral flat feet was not significantly associated with any outcome measures. These findings indicate that bilateral, but not unilateral, flat feet are associated with worse knee pain. A prospective study investigating a causal relationship between bilateral flat feet posture and knee pain as well as disability would be of particular interest to verify the potential adverse effect of altered foot posture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2490-2498, 2017.

Knees with concomitant lateral and mild medial OA may be more symptomatic compared to those without lateral OA. These findings might help to define a clinically distinct subgroup based on a simple radiographic finding in mild knee OA.

Objective: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-b) signaling in the associated mechanism. Design: Rats (n ¼ 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-b signaling.Results: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-b expression and Smad2/3 following TGF-b phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-b expression using ELISA: 4 weeks; P ¼ 0.009, 95% CI [260.1e1340.0]) (p-Smad2/3 expression density: 4 weeks; P ¼ 0.024, 95% CI [1.67e18.27], 8 weeks; P ¼ 0.034, 95% CI [1.25e25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. Conclusions: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.