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1.
Diagnostics (Basel) ; 14(5)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38473040

ABSTRACT

In vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) studies on bone characteristics are limited, partly due to the lack of standardized and objective techniques to describe motion artifacts responsible for lower-quality images. This study investigates the ability of such deep-learning techniques to assess image quality in HR-pQCT datasets of human scaphoids. In total, 1451 stacks of 482 scaphoid images from 53 patients, each with up to six follow-ups within one year, and each with one non-displaced fractured and one contralateral intact scaphoid, were independently graded by three observers using a visual grading scale for motion artifacts. A 3D-CNN was used to assess image quality. The accuracy of the 3D-CNN to assess the image quality compared to the mean results of three skilled operators was between 92% and 96%. The 3D-CNN classifier reached an ROC-AUC score of 0.94. The average assessment time for one scaphoid was 2.5 s. This study demonstrates that a deep-learning approach for rating radiological image quality provides objective assessments of motion grading for the scaphoid with a high accuracy and a short assessment time. In the future, such a 3D-CNN approach can be used as a resource-saving and cost-effective tool to classify the image quality of HR-pQCT datasets in a reliable, reproducible and objective way.

2.
Arch Osteoporos ; 18(1): 142, 2023 11 27.
Article in English | MEDLINE | ID: mdl-38008822

ABSTRACT

The study shows a high incidence of motion artefacts in a central European population and a significant increase of those artefacts with higher age. These findings may impact on the design and conduct of future in vivo HR-pQCT studies or at least help to estimate the potential number of drop outs due to unusable image quality. PURPOSE: Motion artefacts in high-resolution peripheral quantitative computed tomography (HR-pQCT) are challenging, as they introduce error into the resulting measurement data. The aim of this study was to assess the general occurrence of motion artefacts in healthy distal radius and to evaluate the influence of demographic factors. METHODS: The retrospective study is based on 525 distal radius second-generation HR-pQCT scans of 95 patients. All stacks were evaluated by two experienced observers and graded according to the visual grading scale recommended by the manufacturer, ranging from grade 1 (no visible motion artefacts) to grade 5 (severe motion artefacts). Correlations between demographic factors and image quality were evaluated using a linear mixed effects model analysis. RESULTS: The average visual grading was 2.7 (SD ± 0.7). Age and severity of motion artefacts significantly correlated (p = 0.026). Patients aged 65 years or above had an average image quality between grades 1 and 3 in 72.7% of cases, while patients younger than 65 had an average image quality between grades 1 and 3 in 91.9% of cases. Gender, smoking behaviour, and handedness had no significant influence on motion artefacts. CONCLUSION: This study showed a high incidence of motion artefacts in a representative central European population, but also a significant increase of motion artefacts with higher age. This could impact further study designs by planning for a sufficiently large and if possible a more selective study population to gain a representative amount of high-quality image data.


Subject(s)
Artifacts , Tomography, X-Ray Computed , Humans , Retrospective Studies , Tomography, X-Ray Computed/methods , Radius , Demography , Bone Density , Tibia
3.
Quant Imaging Med Surg ; 13(3): 1336-1349, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36915364

ABSTRACT

Background: In-vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) has high potential in scaphoid bone pathologies' scientific and clinical fields. The manufacturer's visual grading scale (VGS) classifies motion artifacts and divides scans into five quality grades ranging from grade 1 (good quality) to grade 5 (poor quality). This prospective study aimed to investigate the feasibility of the VGS and the influence of image quality on bone density and microarchitecture parameters for the scaphoid bone. Methods: Within one year, twenty-two patients with scaphoid fractures received up to six scans of their fractured and contralateral wrist (each consisting of three stacks) using second-generation HR-pQCT (total 256 scans). Three experienced observers graded each stack following the visual grading system, and inter- and intraobserver variability were assessed. The contralateral uninjured scaphoids were then compared pairwise within each patient to high-quality grade 1 scans to determine the influence of image quality on density and microarchitecture parameters. Results: Inter- and intraobserver variability among the three observers significantly revealed fair to moderate agreement, P<0.001 and P<0.05, respectively. Bone volume (BV) fraction tended to increase with poorer image quality but did not exceed four percent. Trabecular bone mineral density (Tb.BMD) decreased with poorer image quality but did not exceed five percent. Trabecular number and trabecular thickness significantly increased by 15.5% and 6.8% at grade five (P<0.001), respectively, and trabecular separation significantly decreased by 13.7% at grade five (P<0.001). Conclusions: This study revealed a considerable influence of motion on bone morphometry parameters of the scaphoid. Therefore, high image quality must be a central point in studies focusing on the histomorphometry of small objects. The high inter- and intraobserver variability limit the VGS. Future research may focus on other grading systems or automated techniques leading to more consistent and reproducible results. Currently, the use of microarchitectural analysis should be limited to cases without motion artefacts or, at most low graded motion artefacts.

4.
Bone ; 166: 116607, 2023 01.
Article in English | MEDLINE | ID: mdl-36368464

ABSTRACT

Image quality degradation due to subject motion confounds the precision and reproducibility of measurements of bone density, morphology and mechanical properties from high-resolution peripheral quantitative computed tomography (HR-pQCT). Time-consuming operator-based scoring of motion artefacts remains the gold standard to determine the degree of acceptable motion. However, due to the subjectiveness of manual grading, HR-pQCT scans of poor quality, which cannot be used for analysis, may be accepted upon initial review, leaving patients with incomplete or inaccurate imaging results. Convolutional Neural Networks (CNNs) enable fast image analysis with relatively few pre-processing requirements in an operator-independent and fully automated way for image classification tasks. This study aimed to develop a CNN that can predict motion scores from HR-pQCT images, while also being aware of uncertain predictions that require manual confirmation. The CNN calculated motion scores within seconds and achieved a high F1-score (86.8 ± 2.8 %), with good precision (87.5 ± 2.7 %), recall (86.7 ± 2.9 %) and a substantial agreement with the ground truth measured by Cohen's kappa (κ = 68.6 ± 6.2 %); motion scores of the test dataset were predicted by the algorithm with comparable accuracy, precision, sensitivity and agreement as by the operators (p > 0.05). This post-processing approach may be used to assess the effect of motion scores on microstructural analysis and can be immediately implemented into clinical protocols, significantly reducing the time for quality assessment and control of HR-pQCT scans.


Subject(s)
Neural Networks, Computer , Tomography, X-Ray Computed , Humans , Reproducibility of Results , Motion , Tomography, X-Ray Computed/methods , Artifacts
5.
J Orthop Surg Res ; 17(1): 503, 2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36403016

ABSTRACT

BACKGROUND: Only few methods treating comminuted radial head fractures have been established providing sufficient joint reconstruction, restoring radial length and enabling early joint mobilization. When an anatomical reconstruction using open reduction and internal fixation is not possible, radial head resection or primary arthroplasty is often conducted. An "Ex situ/on-table" reconstruction is widely disregarded but can be an option. The purpose of this study was to evaluate the functional and radiological outcome of comminuted radial head fractures treated with an "on-table" reconstruction and internal fixation using a low profile plate. METHODS: Fourteen patients who sustained a radial head fracture (9 Mason-Johnston type III and 5 Mason-Johnston type IV) and were treated with an "on-table" reconstruction between 2010 and 2020 were evaluated retrospectively. The patients mean age was 41.3 years (range 21-69). The clinical evaluation included active range of motion, grip strength, pain level and elbow stability. The functional outcome was assessed using the Disability of Arm, Shoulder and the Hand (DASH) score, Mayo Elbow Performance Index (MEPI), Broberg and Morrey score. The radiological examination included a.p. and lateral views of the injured elbow to evaluate nonunions, loss of reduction, joint alignment, avascular radial head necrosis, heterotopic ossifications and posttraumatic osteoarthritis. RESULTS: The inclusion rate was 74% with a mean follow-up of 50 months (range 16-128). The mean elbow flexion of the injured side was 126° (range110-145°) with an average extension loss of 8° (range 0-40°). Pronation was 65° (15-90°) and supination 66° (5-90°). The mean MEPI was 87 points (range 45-100). The mean DASH score was 13 points (range 1-88). According to the Broberg and Morrey functional scoring system, the average score was 92 points (range 88-100). Complete bone union was achieved in 9 cases, partial union in 4 cases and nonunion in one case. There were no signs of avascular necrosis of the radial head. Signs of post-traumatic osteoarthritis were seen in 11 cases. Five patients needed an implant removal due to a radio-ulnar impingement and one patient a revision surgery due to the nonunion and implant breakage. CONCLUSIONS: An on-table (ex situ) reconstruction of the radial head is a reliable option with a good clinical outcome and low complication rate in the surgical treatment of comminuted radial head fractures. It can restore joint alignment and maintain radial length. The risk for avascular necrosis is neglectable, and the bone healing rate is high.


Subject(s)
Fractures, Comminuted , Osteoarthritis , Radius Fractures , Humans , Young Adult , Adult , Middle Aged , Aged , Retrospective Studies , Radius Fractures/diagnostic imaging , Radius Fractures/surgery , Fractures, Comminuted/diagnostic imaging , Fractures, Comminuted/surgery , Necrosis
6.
J Orthop Surg Res ; 17(1): 306, 2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35690778

ABSTRACT

INTRODUCTION: Due to the global COVID-19 pandemic, a ban on sports outside one's home and a prohibition on travel between communities were imposed in spring 2020 in Tyrol, Austria. The aim of this study was to evaluate the impact of these restrictions on a level one trauma center. The objective was to identify the most common injury patterns to ensure targeted prevention in times of an ongoing pandemic. MATERIAL AND METHODS: Patients who presented themselves to our trauma center between weeks 7 and 22 in 2020 were retrospectively compared to a mean of the patients of the three previous years (2017-2019). The evaluated variables were the number of patients, age, gender, country of residence, place of accident, time of treatment, injured body region and anatomical structure, number of surgical intervention and severely injured patients. RESULTS: Comparing the mean count of treated patients per week in 2020 of the pre-lockdown period (n = 804.6) with the lockdown period (n = 201.8) a decrease in admissions by 69.7% could be observed. The admission incidence was 9.9 times higher in previous years than in 2020 during the lockdown period. Among the injuries treated during the lockdown the largest increase in relative numbers was in home injuries, head or face injuries and superficial or penetrating injuries. There was a decrease of seriously injured patients as well as patients that needed surgery during the lockdown compared to previous years. CONCLUSIONS: We observed a significant change in the pattern and volume of injuries during a strict lockdown. Intervention programs to reduce the risk of home injuries should be introduced. Furthermore, in order to save resources during a pandemic, specific guidelines on patient management and treatment should be established for the respective medical specialties. TRIAL REGISTRATION: 1157/2020, 10.12.2020.


Subject(s)
COVID-19 , COVID-19/epidemiology , Communicable Disease Control , Humans , Pandemics/prevention & control , Retrospective Studies , SARS-CoV-2 , Trauma Centers
7.
Arch Orthop Trauma Surg ; 142(5): 887-900, 2022 May.
Article in English | MEDLINE | ID: mdl-35032189

ABSTRACT

INTRODUCTION: The aim of this study was to provide a more precise statement on the outcome after surgical treatment of a bony mallet thumb and possibly give a treatment recommendation regarding the surgical fixation method. PATIENTS AND METHODS: All patients (n = 16) who underwent a surgical treatment for an acute bony mallet thumb fracture between January 2006 and July 2019 were enrolled. The surgical method, complications, the range of motion, tip pinch, lateral key pinch, overall grip strength, visual analog score, Disability of the Arm, Shoulder and Hand Score, Mayo Wrist Score, Patient-Rated Wrist Evaluation Score, Buck-Gramcko Score and radiologic parameters were evaluated. Further, a comprehensive literature search on PubMed was conducted covering a period from 1956 to 2021 to include all possible matching articles on the treatment of the bony mallet thumb (n = 21 articles). RESULTS: Surgical treatment was very inhomogenous including indirect and direct K-wire fixation, screw fixation, plate fixation and anchor fixation methods. The IP joint range of motion and thumb strength ranged from 66 to 94% in comparison to the contralateral side. An open reduction led to worse functional scores compared to a closed reduction. Treatment methods in the literature were also very inhomogenous with a very low patient count, often even pooling data of bony mallet thumb fractures with bony mallet finger fractures. The risk for infection was higher in K-wire fixation methods than in open reduction and internal fixation methods. CONCLUSION: The evidence for the best treatment of a bony mallet thumb fracture is low. On one hand the functional outcome can be inferior using an open reduction approach, but on the other hand, K-wire fixation methods with a closed reduction approach showed a higher risk for infection. Future multi-center research must be conducted to find the best treatment procedure for the best outcome of the patient.


Subject(s)
Finger Injuries , Fractures, Bone , Tendon Injuries , Wrist Injuries , Bone Plates , Bone Wires , Finger Injuries/surgery , Fracture Fixation, Internal/methods , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Humans , Range of Motion, Articular , Thumb/injuries , Treatment Outcome
8.
Arch Orthop Trauma Surg ; 142(2): 343-353, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34338885

ABSTRACT

INTRODUCTION: Recently, the Cobra prostheses were introduced in the treatment of distal radius fractures (DRF) of elderly patients. Fracture prostheses provide an alternative treatment option for complex fractures where conservative therapy seems not acceptable and osteosynthesis seems not possible. Data reporting the feasibility of the Cobra prosthesis are sparse. Therefore, this retrospective follow-up study investigated the clinical and radiological mid-term outcome of the Cobra implant in complex DRFs of elderly patients. MATERIALS AND METHODS: Thirteen patients (mean age 73.5 years, range 65-87 years) were retrospectively evaluated with at least a 1-year follow-up after surgery. Objective and subjective clinical parameters as well as the radiological outcome and complications were analyzed. RESULTS: The mean follow-up period was 31.2 months. Seven cases required a cemented prosthesis. The mean relative range-of-motion compared to the healthy side was 72.3% and 51.8% for extension and flexion, respectively, and 87.9% and 85.7% for pronation and supination, respectively. The mean grip strength was 78.3% compared to the non-operated side. Eight patients were very satisfied, five patients were partly satisfied with the result. The DASH, PRWE, MHQ and Lyon-Scores averaged 39.1, 36.2, 64.9 and 63.3 points, respectively. The mean VAS-Score for pain was 1.1 at rest and 3.2 during activities. Perioperative complications included one dissection of the extensor pollicis longus tendon, one heterotopic ossification, one radiocarpal dislocation and two cases of an ulnar impaction syndrome due to implant subsidence. CONCLUSION: The prosthetic treatment of complex DRFs in elderly patients with the Cobra implant led to clinically and radiologically satisfactory mid-term results. The Cobra prosthesis still does not represent a gold standard but can be regarded as a feasible salvage option for complex DRFs when osteosyntheses may not be possible and non-operative treatment will lead to further functional restrictions and wrist pain during performing activities of daily life in high functional demand patients.


Subject(s)
Radius Fractures , Aged , Aged, 80 and over , Animals , Elapidae , Follow-Up Studies , Fracture Fixation, Internal , Humans , Prostheses and Implants , Radius Fractures/diagnostic imaging , Radius Fractures/surgery , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Wrist Joint
9.
Arch Orthop Trauma Surg ; 142(10): 2659-2667, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34226982

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the difference of the clinical outcome of elderly patients who were treated surgically or conservatively for a displaced olecranon fracture (Mayo type IIA or IIB). PATIENTS AND METHODS: Patients above the age of 70 years who were treated surgically (n = 11) for a displaced Mayo type IIA and IIB olecranon fracture between July 2015 and February 2019 were retrospectively compared with patients who were treated conservatively (n = 6). The range of motion, elbow strength, grip strength, VAS, DASH, OES, MEPI and Broberg and Morrey scores were evaluated. RESULTS: The conservative group showed a non-union with a persistent fracture gap of 17 mm (SD 12 mm) at the articular rim and 31 mm (15 mm) at the dorsal rim while there was no case of non-union in the surgical group. The arch of motion was 120° in the conservative group and 136° in the surgical group. There was no obvious difference in elbow extension strength in comparison to the healthy contralateral side (p = 0.20; 88% group I/87% group II). There was no difference in the OES (p = 0.30; 42 (SD 7) vs. 45 (SD 5)) and MEPI score (p = 0.46; (SD 8) vs. 96 (SD 19)). The conservative group presented a slightly worse DASH [p = 0.10; 26 (SD 25) vs 7 (SD 14)] and a significantly worse Broberg and Morrey score (p = 0.02; 84(SD 9) vs. 95 (SD 7)). The conservative group presented one complication (ulnar nerve palsy), while the surgical group presented two cases (prolonged lymphedema; blocked forearm rotation due to screw length with consecutive revision surgery). CONCLUSION: Widely displaced olecranon fractures can successfully be treated conservatively in low-demanding geriatric patients with a satisfactory outcome. Patient selection is essential as patients that are more active might benefit from surgical treatment. Yet, treatment risks and benefits need to be balanced carefully in regard to the patient`s demands and requests.


Subject(s)
Elbow Joint , Fractures, Bone , Olecranon Process , Ulna Fractures , Aged , Conservative Treatment , Elbow Joint/surgery , Fracture Fixation, Internal/adverse effects , Fractures, Bone/etiology , Humans , Olecranon Process/surgery , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Ulna Fractures/surgery
10.
JBMR Plus ; 5(6): e10493, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34189382

ABSTRACT

Clinical evaluation of fracture healing is often limited to an assessment of fracture bridging from radiographic images, without consideration for other aspects of bone quality. However, recent advances in HRpQCT offer methods to accurately monitor microstructural bone remodeling throughout the healing process. In this study, local bone formation and resorption were investigated during the first year post fracture in both the fractured (n = 22) and contralateral (n = 19) radii of 34 conservatively treated patients (24 female, 10 male) who presented with a unilateral radius fracture at the Innsbruck University Hospital, Austria. HRpQCT images and clinical metrics were acquired at six time points for each patient. The standard HRpQCT image acquisition was captured for all radii, with additional distal and proximal image acquisitions for the fractured radii. Measured radial bone densities were isolated with a voxel-based mask and images were rigidly registered to images from the previous imaging session using a pyramid-based approach. From the registered images, bone formation and resorption volume fractions were quantified for multiple density-based thresholds and compared between the fractured and contralateral radius and relative to demographics, bone morphometrics, and fracture metrics using regression. Compared with the contralateral radius, both bone formation and resorption were significantly increased in the fractured radius throughout the study for nearly all evaluated thresholds. Higher density cortical bone formation continually increased throughout the duration of the study and was significantly greater than resorption during late-stage healing in both the fractured and intact regions of the radius. With the small and diverse study population, only weak relationships between fracture remodeling and patient-specific parameters were unveiled. However this study provides methods for the analysis of local bone remodeling during fracture healing and highlights relevant considerations for future studies, specifically that remodeling postfracture is likely to continue beyond 12-months postfracture. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

11.
Orthop J Sports Med ; 9(1): 2325967120973672, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33457434

ABSTRACT

BACKGROUND: Epidemiological studies on tennis injuries are mainly conducted in either elite professional or junior players. Injury patterns might differ in the recreational tennis player. PURPOSE: To investigate acute injuries in the recreational tennis-playing population with an additional focus on acute injuries that require surgical treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective data analysis was conducted among patients who sustained an acute tennis injury between January 2013 and December 2018 and who had treatment administered at a single university hospital. Demographic data, diagnosis, body region of the trauma, injury mechanism, and treatment methods were recorded. Data were evaluated using descriptive statistics. RESULTS: A total of 449 patients sustained 467 injuries (148 female, 301 male; mean age, 43.6 years; range, 8.2-84.4 years). The injuries occurred throughout the year, with an increased prevalence in the summer months. Injuries occurred in the lower extremity in 59%, the upper extremity in 30%, and the head and trunk in 11%. The main reason for an injury was a twist of a specific joint (n = 194) or a fall (n = 102). Harmless contusion or strains were the most common injury (49%). Ankle sprains were the most common serious injury, occurring in 11% of patients. Fractures occurred in 54 cases (12%). Overall, 9% of patients were treated surgically (fractures, n = 13; meniscal tears, n = 8; Achilles tendon ruptures, n = 6), and surgery was advised to another 1% who did not receive surgery at the study hospital. CONCLUSION: Typical acute injuries in recreational tennis players differ from acute injuries in elite and junior players, with an increased fracture occurrence. The main causes of acute tennis injuries are falls and twists, with 10% of injuries needing surgical treatment, mainly for fractures, meniscal tears, and Achilles tendon ruptures.

12.
Arch Orthop Trauma Surg ; 141(9): 1499-1507, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33040206

ABSTRACT

INTRODUCTION: A new technology (Sportwelding®) was recently presented, which uses ultrasonic energy to meld a resorbable suture anchor at the interface with the host bone. A standardized clinical use was not investigated yet. This study prospectively evaluated the surgical and clinical outcomes of the Fiji Anchor® (Sportwelding®, Schlieren, Switzerland) in the repair of an ulnar collateral ligament lesion of the metacarpophalangeal joint of the thumb. MATERIAL AND METHODS: The range of motion, grip and pinch strength, disability of arm, shoulder and the hand (DASH) and patient rated evaluation (PRWE) score, pain, satisfaction, complications and adverse events were assessed in 24 patients after surgical treatment for an acute displaced rupture or avulsion of the ulnar collateral metacarpophalangeal ligament of the thumb using the Fiji Anchor® after 6, 12 and 52 weeks. RESULTS: At final follow up, the range of motion of the metacarpophalangeal joint reached almost the contralateral side (49.3° SD 11.7°). Thumb opposition showed a Kapandji score of 9.7 (SD 0.5; range 9-10). Grip strength, the lateral, tip and the three jaw pinch showed nearly similar values compared to the contralateral side (83-101%). Pain was low (0.2 SD 0.7 at rest and 0.6 SD 1.0 during load). The DASH score was 5.0 (SD 7.3) and the PRWE score was 4.1 (SD 9.0). 81% of patients were very satisfied at final follow-up. Two patients were rated unstable during the follow-up period due to a second traumatic event. Three cases experienced difficulties during anchor insertion, whereby incorrect anchor insertion resulted in damage to the suture material; however, this was resolved after additional training. CONCLUSION: One advantage of this anchor appears to be its stable fixation in cancellous bone. The surgical treatment of an ulnar collateral ligament lesion of the thumb using the Fiji Anchor® can lead to an excellent clinical outcome with a minor complication rate; however, long-term dangers and the cost effectiveness of the procedure are not known yet.


Subject(s)
Collateral Ligament, Ulnar , Thumb , Follow-Up Studies , Humans , Metacarpophalangeal Joint/surgery , Thumb/surgery
13.
Handchir Mikrochir Plast Chir ; 52(5): 392-398, 2020 Sep.
Article in German | MEDLINE | ID: mdl-32992396

ABSTRACT

The aim of the present study is to give an overview over the possibilities of 3D imaging in the analysis of scaphoid fractures and non-unions and to discuss them on the base of case studies and literature.


Subject(s)
Radius Fractures , Scaphoid Bone/diagnostic imaging , Scaphoid Bone/surgery , Ulna Fractures , Wrist Injuries/diagnostic imaging , Wrist Injuries/surgery , Humans , Imaging, Three-Dimensional
14.
Cell Death Dis ; 9(5): 470, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29686375

ABSTRACT

Growth factor withdrawal induces rapid apoptosis via mitochondrial outer membrane permeabilization. We had previously observed that cell death of IL-3-dependent Ba/F3 cells, induced by removal of the growth factor, required the activity of the kinase GSK-3. Employing CRISPR/Cas9-mediated gene knockout, we aimed to identify pro-apoptotic GSK-3 regulated factors in this process. Knockout of either Puma or Bim demonstrated that the induction of Puma, but not Bim, was crucial for apoptosis induced by IL-3 deprivation. Thus, we aimed at identifying the GSK-3-dependent PUMA regulator. Loss of FOXO3A reduced the induction of Puma, while additional loss of p53 completely repressed induction upon growth factor withdrawal. A constitutively active mutant of FOXO3A, which cannot be controlled by AKT directly, still required active GSK-3 for the full transcriptional induction of Puma and cell death upon IL-3 withdrawal. Thus, the suppression of GSK-3 is the key function of PI3K signaling in order to prevent the induction of Puma by FOXO3A and p53 and thereby apoptosis upon growth factor withdrawal.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis , Glycogen Synthase Kinase 3/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Signal Transduction , Apoptosis Regulatory Proteins/genetics , Glycogen Synthase Kinase 3/genetics , HCT116 Cells , HEK293 Cells , Humans , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins/genetics
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