Erratum to: Development of a clinical risk score for pain and function following total knee arthroplasty: results from the TRIO study.

[This corrects the article DOI: 10.1093/rap/rky021.][This corrects the article DOI: 10.1093/rap/rky021.].

FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition.

Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5' and 3' ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17-3p/miR-127-5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks.

Development of a clinical risk score for pain and function following total knee arthroplasty: results from the TRIO study.

OBJECTIVES: The aim was to develop and validate a simple clinical prediction model, based on easily collected preoperative information, to identify patients at high risk of pain and functional disability 6 months after total knee arthroplasty (TKA). METHODS: This was a multicentre cohort study of patients from nine centres across the UK, who were undergoing a primary TKA for OA. Information on sociodemographic, psychosocial, clinical and quality-of-life measures were collected at recruitment. The primary outcome measure for this analysis was the Oxford knee score (OKS), measured 6 months postoperatively by postal questionnaire. Multivariable logistic regression was used to develop the model. Model performance (discrimination and calibration) and internal validity were assessed, and a simple clinical risk score was developed. RESULTS: Seven hundred and twenty-one participants (mean age 68.3 years; 53% female) provided data for the present analysis, and 14% had a poor outcome at 6 months. Key predictors were poor clinical status, widespread body pain, high expectation of postoperative pain and lack of active coping. The developed model based on these variables demonstrated good discrimination. At the optimal cut-off, the final model had a sensitivity of 83%, specificity of 61% and positive likelihood ratio of 2.11. Excellent agreement was found between observed and predicted outcomes, and there was no evidence of overfitting in the model. CONCLUSION: We have developed and validated a clinical prediction model that can be used to identify patients at high risk of a poor outcome after TKA. This clinical risk score may be an aid to shared decision-making between patient and clinician.

Growth kinetics of rat mesenchymal stem cells from 3 potential sources: bone marrow, periosteum and adipose tissue.

OBJECTIVE: Mesenchymal stem cells (MSCs) have potential in orthopaedic applications as they are able to differentiate into bone and cartilage. These cells can be isolated from a variety of adult tissues. Three sources that are relevant for orthopaedic applications are bone marrow, periosteum and adipose tissue. The purpose of the present study was to compare the growth kinetics and colony forming potency of rat MSCs from these sources. MATERIAL AND METHOD: Bone marrow from the femur periosteum from the femoral diaphysis and adipose tissue from the inguinal area of Wistar rats were harvested for MSC isolation. The cells from 2nd-4th passage from primary culture were selected for study of their growth curves, population doubling time and colony forming ability using the percentage of colony forming units and colony forming area as the outcome measure. RESULTS: The isolated cells from these 3 sources were capable of osteogenesis, chondrogenesis and adipogenesis. The growth kinetics were compared using the growth curve and the population doubling time (PDT): bone marrow derived cells (PDT = 3.99 days, SD = 1.19) and periosteum derived cells (PDT = 3.55 days, SD = 1.21) had faster growth kinetics than adipose derived cells (PDT = 4.65 days, SD = 1.53). The percentage of colony forming units and the colony forming area from bone marrow derived cells (% colony forming unit = 8.58, SD = 1.35 and % colony forming area = 25.12, SD = 7.31) and periosteum derived cells (% colony forming units = 9.92, SD = 2.06, % colony forming area = 32.45, SD = 10.74) were significantly greater (p < 0. 05) than adipose derived cells (% colony forming units = 5.92, SD = 0.78, % colony forming area = 15.80, SD = 9.035). CONCLUSION: The growth kinetics and colony forming potency of MSCs from bone marrow and periosteum were comparable. The bone marrow and periosteum should be a suitable source for MSC isolation. The growth kinetics of MSCs derived from adipose tissue was lower than the other sources. Adipose tissue can be used as an alternative source as it is readily available and dispensable.

3D freehand ultrasound for in vivo determination of human skeletal muscle volume.

Skeletal muscle volume is an important indicator of muscle function. Three-dimensional (3D) freehand ultrasound provides a noninvasive method for determining muscle volume and is acquired using a standard clinical ultrasound machine and an external tracking system to monitor transducer position. Eleven healthy volunteers were scanned with a 3D freehand system that uses an optical tracking device. Interest was concentrated on one of the muscles of the quadriceps group, rectus femoris and volume measurements performed on 30 mm cross-sections were compared with measurements derived from magnetic resonance imaging. Measured muscle volumes ranged from 5 cm(3) to 28 cm(3). The mean difference between measurements from 3D freehand ultrasound and magnetic resonance was 0.53 cm(3) with 95% limits of agreement of +/-2.14 cm(3). Muscle volume measurements obtained using 3D ultrasound were within +/-16% of the corresponding value from magnetic resonance imaging. We have shown for the first time that 3D freehand ultrasound can be used to determine human skeletal muscle volume accurately in vivo.