Cartilage is a tissue with limited self-healing potential. Hence, cartilage defects require surgical attention to prevent or postpone the development of osteoarthritis. For cell-based cartilage repair strategies, in particular autologous chondrocyte implantation, articular chondrocytes are isolated from cartilage and expanded in vitro to increase the number of cells required for therapy. During expansion, the cells lose the competence to autonomously form a cartilage-like tissue, that is in the absence of exogenously added chondrogenic growth factors, such as TGF-βs. We hypothesized that signaling elicited by autocrine and/or paracrine TGF-β is essential for the formation of cartilage-like tissue and that alterations within the TGF-β signaling pathway during expansion interfere with this process. Primary bovine articular chondrocytes were harvested and expanded in monolayer culture up to passage six and the formation of cartilage tissue was investigated in high density pellet cultures grown for three weeks. Chondrocytes expanded for up to three passages maintained the potential for autonomous cartilage-like tissue formation. After three passages, however, exogenous TGF-β1 was required to induce the formation of cartilage-like tissue. When TGF-β signaling was blocked by inhibiting the TGF-β receptor 1 kinase, the autonomous formation of cartilage-like tissue was abrogated. At the initiation of pellet culture, chondrocytes from passage three and later showed levels of transcripts coding for TGF-β receptors 1 and 2 and TGF-β2 to be three-, five- and five-fold decreased, respectively, as compared to primary chondrocytes. In conclusion, the autonomous formation of cartilage-like tissue by expanded chondrocytes is dependent on signaling induced by autocrine and/or paracrine TGF-β. We propose that a decrease in the expression of the chondrogenic growth factor TGF-β2 and of the TGF-β receptors in expanded chondrocytes accounts for a decrease in the activity of the TGF-β signaling pathway and hence for the loss of the potential for autonomous cartilage-like tissue formation.

For autologous chondrocyte transplantation, articular chondrocytes are harvested from cartilage tissue and expanded in vitro in monolayer culture. We aimed to characterize with a cellular resolution the synthesis of collagen type II (COL2) and collagen type I (COL1) during expansion in order to further understand why these cells lose the potential to form cartilage tissue when re‐introduced into a microenvironment that supports chondrogenesis. During expansion for six passages, levels of transcripts encoding COL2 decreased to <0.1%, whereas transcript levels encoding COL1 increased 370‐fold as compared to primary chondrocytes. Flow cytometry for intracellular proteins revealed that chondrocytes acquired a COL2/COL1‐double positive phenotype during expansion, and the COL2 positive cells were able to enter the cell cycle. While the fraction of COL2 positive cells decreased from 70% to <2% in primary chondrocytes to passage six cells, the fraction of COL1 positive cells increased from 95%. In parallel to the decrease of the fraction of COL2 positive cells, the cells' potential to form cartilage‐like tissue in pellet cultures steadily decreased. Intracellular staining for COL2 enables for characterization of chondrocyte lineage cells in more detail with a cellular resolution, and it may allow predicting the effectiveness of expanded chondrocytes to form cartilage‐like tissue. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1503–1511, 2014.

A rotator cuff tear (RCT) is a common shoulder diagnosis and its etiology may be acute, traumatic, or chronic degenerative. Differentiation between the 2 etiologies may be important for multiple reasons, but remains difficult based on imaging. Further knowledge about radiographic and magnetic resonance findings to distinguish traumatic from degenerative RCT is needed. We analyzed magnetic resonance arthrograms (MRAs) of 96 patients with traumatic or degenerative superior RCT, which were matched according their age and the affected rotator cuff muscle into the 2 groups. Patients older than 66 years of age were excluded from the study to avoid including cases with pre-existing degeneration. In the case of traumatic RCT, the time between the trauma and MRA had to be less than 3 months. Various parameters of the supraspinatus (SSP) muscle-tendon unit were assessed (tendon thickness, presence of a remaining tendon stump at the greater tubercle, magnitude of retraction, layer appearance). The retraction of the 2 SSP layers were individually measured to determine the difference of retraction. Additionally, edema of the tendon and muscle, the tangent- and kinking-sign as well as the newly introduced Cobra-sign (bulging of the distal part of the ruptured tendon with slim configuration of the medial part of the tendon) were analyzed. Edema within the SSP muscle (sensitivity 13%, specificity 100%, P = .011) or the tendon (sensitivity 86%, specificity 36%, P = .014) are more frequent in traumatic RCT. The same association was found for the kinking-sign (sensitivity 53%, specificity 71%, P = .018) and the Cobra sign (sensitivity 47%, specificity 84%, P = .001). Even though not statistically significant, tendencies were observed toward thicker tendon stumps in traumatic RCT, and greater difference in retraction between the 2 SSP layers in the degenerative group. The cohorts had no difference in the presence of a tendon stump at the greater tuberosity. Muscle and tendon edema, as well as tendon kinking appearance and the newly introduced cobra-sign are suitable MRA parameters to distinguish between traumatic and degenerative etiology of a superior RTC.

The estimation of BMD with CT scans requires a calibration method, usually based on a phantom. In asynchronous calibration, the phantom is scanned separately from the patient. A standardized acquisition protocol must be used to avoid variations between patient and phantom. However, variations can still be induced, for example, by temporal fluctuations or patient characteristics. Based on the further use of 739 forensic and 111 clinical CT scans, this study uses the proximal femur BMD value (“total hip”) to assess asynchronous calibration accuracy, using in-scan calibration as ground truth. It identifies the parameters affecting the calibration accuracy and quantifies their impact. For time interval and table height, the impact was measured by calibrating the CT scan twice (once using the phantom scan with closest acquisition parameters and once using a phantom scan with standard values) and comparing the calibration accuracy. For other parameters such as body weight, the impact was measured by computing a linear regression between parameter values and calibration accuracy. Finally, this study proposes correction methods to reduce the effect of these parameters and improve the calibration accuracy. The BMD error of the asynchronous calibration, using the phantom scan with the closest acquisition parameters, was −1.2 ± 1.7% for the forensic and − 1.6 ± 3.5% for the clinical dataset. Among the parameters studied, time interval and body weight were identified as the main sources of error for asynchronous calibration, followed by table height and reconstruction kernel. Based on these results, a correction method was proposed to improve the calibration accuracy.

The gull sign, representing superomedial dome impaction in acetabular fractures, was first described approximately 20 years ago by Anglen and co-workers. They concluded that this sign equates with poor outcomes after open reduction and internal fixation (ORIF), terming it a "harbinger for failure". Since then, the presence of the gull sign has frequently influenced surgical decision-making in geriatric acetabular fractures. The aim of this radiological descriptive study was to revisit the accuracy of the gull sign seen on pelvic radiographs in predicting dome impaction on computed tomography (CT). In a retrospective study, conventional pelvic radiographs and CT scans of n = 201 patients (mean age±SD: 68±17y, 75 % male) with acetabular fractures treated surgically between 2009 and 2020 were analyzed. The presence of the gull sign was assessed on anteroposterior pelvic radiographs. CT scans were assessed for true impaction ("brick sign") with focus on the acetabular surface and compared to the findings according to Anglen`s description. The gull sign was noted on pelvic radiographs in 49 of 201 cases (24 %). In 28 out of these 49 cases (57 %) a dome impaction was noted on CT. In the remaining 21 cases (43 %), CT revealed no actual impaction but rather an elevated dome following displaced fracture fragments. Conversely, among the 152 patients (76 %) without a gull sign, CT identified previously undetected dome impactions in 41 cases. Overall, the gull sign had a sensitivity of 41 %, a specificity of 84 %, and a positive predictive value of 57 % for detecting dome impactions. The gull sign is an unreliable predictor for dome impaction in acetabular fractures for the following reasons: in the presence of the gull sign nearly half of the cases an elevated fragment only (not an impacted fragment) was noted on CT; despite an absence of the gull sign in nearly one-third of these cases dome impactions ("brick sign") were present on CT. Consequently, routine preoperative CT imaging is essential to accurately differentiate true dome impactions ("brick sign") from dome elevation, thereby guiding appropriate surgical decision-making between "disimpaction versus reduction" and in general between the "fix or replace" debate.