Adaptation of the protein translational apparatus during ATDC5 chondrogenic differentiation.

IntroductionRibosome biogenesis is integrated with many cellular processes including proliferation, differentiation and oncogenic events. Chondrogenic proliferation and differentiation require a high cellular translational capacity to facilitate cartilaginous extracellular matrix production. We here investigated the expression dynamics of factors involved in ribosome biogenesis during in vitro chondrogenic differentiation and determined whether protein translation capacity adapts to different phases of chondrogenic differentiation.MaterialsSnoRNA expression during ATDC5 differentiation was analyzed by RNA sequencing of samples acquired from day 0 (progenitor stage), 7 (chondrogenic stage) and day 14 (hypertrophic stage). RT-qPCR was used to determine expression of fibrillarin, dyskerin, UBF-1, Sox9, Col2a1, Runx2, Col10a1 mRNAs and 18S, 5.8S and 28S rRNAs. Protein expression of fibrillarin, dyskerin and UBF-1 was determined by immunoblotting. Ribosomal RNA content per cell was determined by calculating rRNA RT-qPCR signals relative to DNA content (SYBR Green assay). Total protein translational activity was evaluated with a puromycilation assay and polysome profiling.ResultsAs a result of initiation of chondrogenic differentiation (Δt0-t7), 21 snoRNAs were differentially expressed (DE). Hypertrophic differentiation caused DE of 23 snoRNAs (Δt7-t14) and 43 when t0 was compared to t14. DE snoRNAs, amongst others, target nucleotide modifications in the 28S rRNA peptidyl transferase center and the 18S rRNA decoding center. UBF-1, fibrillarin and dyskerin expression increased as function of differentiation and displayed highest fold induction at day 5-6 in differentiation. Ribosomal RNA content per cell was significantly increased at day 7, but not at day 14 in differentiation. Similar dynamics in translational capacity and monosomal ribosome fraction were observed during differentiation.ConclusionThe expression of a great number of ribosome biogenesis factors is altered during chondrogenic differentiation of ATDC5 cells, which is accompanied by significant changes in cellular translational activity. This elucidation of ribosome biogenesis dynamics in chondrogenic differentiation models enables the further understanding of the role of ribosome biogenesis and activity during chondrocyte cell commitment and their roles in human skeletal development diseases

Time-lapse technic used to uncover the naturel growth of osteochondromas of the wrist in patients with Hereditary Multiple Osteochondromas

Background: In patients with Hereditary Multiple Osteochondromas (HMO) shortening and deformity of the long bones is a well-known sequel. Several theories could clarify the cause of shortening or deformity. Methods: To reveal the development of the long bones and the influence of the osteochondromas on the growth we used time-lapse technique. Radiographic images, taken for clinical reasons, of 6 HMO affected patients with known osteochondromas on the distal end of the lower arm were selected and adapted to make them suitable for use with a time-lapse technique. The images were placed in chronological order. The ulnar shortening, lunate position and radial inclination were registered, as were the clinical problems. The hypothesis being that slow occurring developmental deformities are easier comprehended and qualitatively studied when the changes are accelerated. Results: None of the patients had radial head dislocation at the elbow. The majority of the wrists had decreased ulnar length and increased radial inclination. The clinical problems were limited. The osteochondromatic growth did not seem related to the wrist growth, but when the inclination of the radius was steep osteochondromas were present in the distal radius and the ulna was shortened. Some osteochondromas disappeared. Conclusions: Time-lapse videos of wrists of patients with HMO showed no relation between growth of wrists and osteochondromas but it did show osteochondromas disappearing. A steep radial inclination seems related to ulnar shortening and might be due to proximity of radial osteochondromas. Patients had marked radiological changes, but relatively few clinical problems

Windswept Deformity a Disease or a Symptom?:A Systematic Review on the Aetiologies and Hypotheses of Simultaneous Genu Valgum and Varum in Children

OBJECTIVE: The objective of this study is to create an overview of the possible aetiologies of windswept deformity and to emphasize the points of attention when presented with a case. METHODS: A systematic search according to the PRISMA statement was conducted using PubMed, African Journals Online, Cochrane, Embase, Google Scholar, and Web of Science. Articles investigating the aetiology of windswept deformity at the knee in children, and articles with windswept deformity as an ancillary finding were included. The bibliographic search was limited to English-language articles only. The level of evidence and methodological appraisal were assessed. RESULTS: Forty-five articles discussing the aetiology of windswept deformity were included. A variety of aetiologies can be brought forward. These can be divided into the following groups: 'Rickets and other metabolic disorders', 'skeletal dysplasias and other genetic disorders', 'trauma' and 'descriptive articles without specific underlying disorder'. With rickets being the largest group. Interestingly, in the group without a specific underlying disorder, all patients were from African descent, being otherwise healthy and presented with windswept deformity between two and three years of age. CONCLUSION: We have presented an overview that may help identify the underlying disorder in children with windswept deformity. A step-by-step guide for clinicians who see a child with windswept deformity is provided. Even though, according to the Oxford level of evidence, most articles have a low level of evidence

Active monitoring versus immediate abduction as treatment of stable developmental dysplasia of the hip: a systematic review of the literature

OBJECTIVES: This systematic review aims to compare the effects of active monitoring and abduction treatment on the Graf alpha angle, Acetabular Index (AI) and femoral head coverage in infants with stable developmental dysplasia of the hip (DDH). DESIGN: Systematic review reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: A search of the PubMed, Embase, Cochrane and Web of Science databases was performed in January 2020 and updated in January 2021. ELIGIBILITY CRITERIA: (Non-)randomised studies comparing active monitoring with abduction treatment in infants younger than 4 months with stable DDH were included. DATA EXTRACTION AND SYNTHESIS: All eligible articles were methodologically assessed using the Cochrane risk of bias tools. Data were extracted by summarising the study characteristics and results. RESULTS: Of the six included studies, two randomised studies were of low risk and two of some concerns. Two non-randomised studies were of serious risk. In total, 544 dysplastic hips (439 infants) were investigated, of which 307 were observed and 237 were treated. Two studies reported a faster improvement of the alpha angle and average acetabular coverage in treated hips at 3 months. No differences in AI between the treatment and observation group after 3 months were reported. In total, 38 infants (12%) in the observation group switched to the treatment group. At the final radiograph, 21 observed hips and 32 treated hips were dysplastic. CONCLUSIONS: There were no differences in AI between the treatment and observation group after 3 months in infants up to 4 months of age with stable DDH hips. The switch of 38 infants (12%) from the observation to the treatment group corroborates that not all infantile DDH hips will spontaneously progress into normal hips. The small study population sizes and methodological heterogeneity warrant a large randomised controlled trial to study this research question. PROSPERO REGISTRATION NUMBER: CRD4202123300

Active monitoring versus immediate abduction as treatment of stable developmental dysplasia of the hip:a systematic review of the literature

OBJECTIVES: This systematic review aims to compare the effects of active monitoring and abduction treatment on the Graf alpha angle, Acetabular Index (AI) and femoral head coverage in infants with stable developmental dysplasia of the hip (DDH). DESIGN: Systematic review reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: A search of the PubMed, Embase, Cochrane and Web of Science databases was performed in January 2020 and updated in January 2021. ELIGIBILITY CRITERIA: (Non-)randomised studies comparing active monitoring with abduction treatment in infants younger than 4 months with stable DDH were included. DATA EXTRACTION AND SYNTHESIS: All eligible articles were methodologically assessed using the Cochrane risk of bias tools. Data were extracted by summarising the study characteristics and results. RESULTS: Of the six included studies, two randomised studies were of low risk and two of some concerns. Two non-randomised studies were of serious risk. In total, 544 dysplastic hips (439 infants) were investigated, of which 307 were observed and 237 were treated. Two studies reported a faster improvement of the alpha angle and average acetabular coverage in treated hips at 3 months. No differences in AI between the treatment and observation group after 3 months were reported. In total, 38 infants (12%) in the observation group switched to the treatment group. At the final radiograph, 21 observed hips and 32 treated hips were dysplastic. CONCLUSIONS: There were no differences in AI between the treatment and observation group after 3 months in infants up to 4 months of age with stable DDH hips. The switch of 38 infants (12%) from the observation to the treatment group corroborates that not all infantile DDH hips will spontaneously progress into normal hips. The small study population sizes and methodological heterogeneity warrant a large randomised controlled trial to study this research question. PROSPERO REGISTRATION NUMBER: CRD4202123300

Gait analysis of foot compensation in symptomatic Hallux Rigidus patients

BACKGROUND: Compensatory motion of foot joints in hallux rigidus (HR) are not fully known. This study aimed to clarify the kinematic compensation within the foot and to detect whether this affects plantar pressure distribution. METHODS: Gait characteristics were assessed in 16 patients (16 feet) with HR and compared with 15 healthy controls (30 feet) with three-dimensional gait analysis by using the multi-segment Oxford Foot Model, measuring spatio-temporal parameters, joint kinematics and plantar pressure. RESULTS: HR subjects showed less hallux plantar flexion during midstance and less hallux dorsiflexion during push-off, while increased forefoot supination was detected during push-off. No significant differences in plantar pressure were detected. Step length was significantly smaller in HR subjects, while gait velocity was comparable between groups. CONCLUSIONS: HR significantly affects sagittal hallux motion, and the forefoot compensates by an increased supination during push-off. Despite this kinematic compensatory mechanism, no significant differences in plantar loading were detected

Metallic hemiarthroplasty or arthrodesis of the first metatarsophalangeal joint as treatment for hallux rigidus:A systematic review and meta-analysis

BACKGROUND: Arthrodesis and metallic hemiarthroplasty are two surgical interventions for the treatment of end-stage osteoarthritis of the first metatarsophalangeal (MTP1) joint. This systematic review and meta-analysis aims to compare the two operations with regards to patient-reported outcomes, pain reduction, complications and revision rates. METHODS: A systematic literature search identified all relevant studies. The methodological quality was assessed using two validated tools. Data of interest were derived and presented. For non-comparative studies, data was assessed for trends, while for comparative studies pooling statistics were performed. RESULTS: A total of 33 studies were included for analysis. The majority of studies (>75%) reported an AOFAS-HMI score greater than 80 points after both metallic hemiarthroplasty and arthrodesis. The lowest VAS pain score was observed after arthrodesis (weighted mean difference -1.58, 95% confidence interval (CI) -2.16 to -1.00 P< 0.00001). Comparable numbers of complications (odds radio 1.48, 95% CI 0.81 to 2.73, P = 0.21, favoring: hemiarthroplasty) and revisions (odds ratio 1.16, 95% CI 0.62 to 2.15 P = 0.64, favoring: hemiarthroplasty) were observed after both interventions. The included non-comparative studies seem to confirm these findings of the comparative studies. CONCLUSION: Metallic hemiarthroplasty and arthrodesis have excellent clinical outcomes and acceptable complication- and revision rates. Arthrodesis seems to be superior in pain reduction, while metallic hemiarthroplasty is a suitable alternative for patients performing activities that requires motion in the first metatarsophalangeal joint