Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

Imaging of sports injuries in adolescents.

Musculoskeletal injuries in adolescents tend to occur in particular locations and have distinct characteristics, as they affect an immature skeleton. Increased engagement in sports, extended training and competition periods, and early specialization in specific sports, among other factors, have contributed significantly to the rise in musculoskeletal sports injuries in adolescents. Furthermore, females show a particularly pronounced increase in sports participation, where anatomical and hormonal factors play crucial roles in the development and increased frequency of sports-related injuries. Consequently, there is a growing demand for diagnostic imaging techniques. Musculoskeletal and pediatric radiologists require a comprehensive understanding of intrinsic and extrinsic risk factors and the successive stages of skeletal development that can influence the specific characteristics of sports injuries in adolescents. These aspects are crucial for the diagnostic, prognostic, and therapeutic management of these injuries and for mitigating chronic conditions that could compromise future sports participation. This review analyzes the primary musculoskeletal injuries in adolescent athletes and highlights the pivotal role of different imaging methods in their diagnosis and management.

How to avoid genu recurvatum in leg-length discrepancy treated with tension-band plates. A volumetric magnetic resonance analysis.

Aims and objectives: Genu recurvatum deformity after treatment of leg-length discrepancy (LLD) with tension-band plating is a recognized, but poorly described phenomenon in medical literature. The aim of this study was to evaluate clinical and radiological features of patients treated with tension-band plating for LLD assessing the development of a recurvatum deformity and its relationship to plate and screw disposition in a transversal plane, thus attempting to establish optimal plate positioning. Materials and methods: Retrospective study of children with LLD treated with tension-band plating. Primary endpoints were clinical and radiological knee recurvatum and anterior and posterior physeal areas measured drawing a line spanning from the lateral to the medial tension-band plates in the transverse plane using volumetric magnetic resonance imaging (vMRI). These findings were compared between patients with and without knee recurvatum. Results: Twelve children (mean age 11.7 years) were included. Average follow-up was 2.6 years (1.5-5.0). Tension-band plating led to a significant reduction in LLD (mean, 15 mm). Six patients (50 %) developed clinical genu recurvatum (mean, 22°). According to vMRI, patients with genu recurvatum had a larger posterior to anterior physeal area ratio in both distal femur (1.6 versus 0.9, p < 0.05) and proximal tibial physes (2.2 versus 1.0, p < 0.05). Conclusion: The optimal position of the tension-band plates in distal femoral and proximal tibial physes should be in a point where a posterior to anterior physeal areas ratio is around 1.0, so as to achieve an even distribution of the physeal areas in the multidimensional physeal transverse plane. This point anatomically corresponds in the sagittal X-ray view to an imaginary line located just anterior to the posterior diaphyseal cortical bone on a true lateral radiograph for both femur and tibia.

Increased knee flexion in participants with cerebral palsy results in altered stresses at the distal femoral growth plate compared to a typically developing cohort.

INTRODUCTION: Femoral deformities are highly prevalent in children with cerebral palsy (CP) and can have a severe impact on patients' gait abilities. While the mechanical stress regime within the distal femoral growth plate remains underexplored, understanding it is crucial given bone's adaptive response to mechanical stimuli. We quantified stresses at the distal femoral growth plate to deepen our understanding of the relationship between healthy and pathological gait patterns, internal loading, and femoral growth patterns. METHODS: This study included three-dimensional motion capture data and magnetic resonance images of 13 typically developing children and twelve participants with cerebral palsy. Employing a multi-scale mechanobiological approach, integrating musculoskeletal simulations and subject-specific finite element analysis, we investigated the orientation of the distal femoral growth plate and the stresses within it. Limbs of participants with CP were grouped depending on their knee flexion kinematics during stance phase as this potentially changes the stresses induced by knee and patellofemoral joint contact forces. RESULTS: Despite similar growth plate orientation across groups, significant differences were observed in the shape and distribution of growth values. Higher growth rates were noted in the anterior compartment in CP limbs with high knee flexion while CP limbs with normal knee flexion showed high similarity to the group of healthy participants. DISCUSSION: Results indicate that the knee flexion angle during the stance phase is of high relevance for typical bone growth at the distal femur. The evaluated growth rates reveal plausible results, as long-term promoted growth in the anterior compartment leads to anterior bending of the femur which was confirmed for the group with high knee flexion through analyses of the femoral geometry. The framework for these multi-scale simulations has been made accessible on GitHub, empowering peers to conduct similar mechanobiological studies. Advancing our understanding of femoral bone development could ultimately support clinical decision-making.

Pediatric Trauma.

Pediatric foot and ankle trauma includes a range of injuries affecting the lower extremities in children, typically aged from infancy to adolescence. These incidents can arise from various causes, including sports-related accidents, falls, and high-velocity injuries. Due to the dynamic growth and development of bones and soft tissues in pediatric patients, managing these injuries requires specialized knowledge and care. Early diagnosis and appropriate treatment are crucial to ensure optimal recovery and prevent potential long-term consequences. Treatment depends on severity and type of injury but may involve a combination of immobilization, physical therapy, or surgical intervention.

Detection of early metaphyseal changes in a piglet model of Legg-Calvé-Perthes disease using quantitative mapping of MRI relaxation times.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast-enhanced MRI in n = 10 6-week-old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast-enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral-control femoral heads using paired t-tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: -13.3 ± 9.3 ms, p = 0.013; -32 ± 23 ms, p < 0.001; -43 ± 41 ms, p = 0.009; and -39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD.

Inadequate linear catch-up growth in children born small for gestational age: Influencing factors and underlying mechanisms.

A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.

Ex vivo organotypic bone slice culture reveals preferential chondrogenesis after sustained growth plate injury.

Postnatal bone growth primarily relies on chondrocyte proliferation and osteogenic differentiation within the growth plate (GP) via endochondral ossification. Despite its importance, the GP is vulnerable to injuries, affecting 15-30 % of bone fractures. These injuries may lead to growth discrepancies, influence bone length and shape, and negatively affecting the patient's quality of life. This study aimed to investigate the molecular and cellular physiological and pathophysiological regeneration following sustained growth plate injury (GPI) in an ex vivo rat femur organotypic culture (OTC) model. Specifically, focusing on postnatal endochondral ossification process. 300 µm thick ex vivo bone cultures with a 2 mm long horizontal GPI was utilized. After 15 days of cultivation, gene expression analysis, histological and immunohistochemistry staining's were conducted to analyze key markers of endochondral ossification. In our OTCs we observed a significant increase in Sox9 expression due to GPI at day 15. The Ihh-PTHrP feedback loop was affected, favoring chondrocyte proliferation and maturation. Ihh levels increased significantly on day 7 and day 15, while PTHrP was downregulated on day 7. GPI had no impact on osteoclast number and activity, but gene expression analysis indicated OTCs' efforts to inhibit osteoclast differentiation and activation, thereby reducing bone resorption. In conclusion, our study provides novel insights into the molecular and cellular mechanisms underlying postnatal bone growth and regeneration following growth plate injury (GPI). We demonstrate that chondrocyte proliferation and differentiation play pivotal roles in the regeneration process, with the Ihh-PTHrP feedback loop modulating these processes. Importantly, our ex vivo rat femur organotypic culture model allows for the detailed investigation of these processes, providing a valuable tool for future research in the field of skeletal biology and regenerative medicine.

Generalizing Diffusion Tensor Imaging of the Physis and Metaphysis.

BACKGROUND: Current methods to predict height potential are inaccurate. Predicting height by using MRI of the physeal cartilage has shown promise but the applicability of this technique in different imaging setups has not been well-evaluated. PURPOSE: To assess variability in diffusion tensor imaging of the physis and metaphysis (DTI-P/M) of the distal femur between different scanners, imaging parameters, tractography software, and resolution. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Eleven healthy subjects (five males and six females ages 10-16.94). FIELD STRENGTH/SEQUENCE: 3 T; DTI single shot echo planar sequences. ASSESSMENT: Physeal DTI tract measurements of the distal femur were compared between different scanners, imaging parameters, tractography settings, interpolation correction, and tractography software. STATISTICAL TESTS: Bland-Altman, Spearman correlation, linear regression, and Shapiro-Wilk tests. Threshold for statistical significance was set at P = 0.05. RESULTS: DTI tract values consistently showed low variability with different imaging and analysis settings. Vendor to vendor comparison exhibited strong correlation (ρ = 0.93) and small but significant bias (bias -5.76, limits of agreement [LOA] -24.31 to 12.78). Strong correlation and no significant difference were seen between technical replicates of the General Electric MRI scanner (ρ = 1, bias 0.17 [LOA -1.5 to 1.2], P = 0.42) and the Siemens MRI scanner (ρ = 0.89, bias = 0.56, P = 0.71). Different voxel sizes (1 × 1 × 2 mm3 vs. 2 × 2 × 3 mm3) did not significantly affect DTI values (bias = 1.4 [LOA -5.7 to 8.4], P = 0.35) but maintained a strong correlation (ρ = 0.82). Gap size (0 mm vs. 0.6 mm) significantly affects tract volume (bias = 1.8 [LOA -5.4 to 1.8]) but maintains a strong correlation (ρ = 0.93). Comparison of tractography algorithms generated significant differences in tract number, length, and volume while maintaining correlation (ρ = 0.86, 0.99, 0.93, respectively). Comparison of interobserver variability between different tractography software also revealed significant differences while maintaining high correlation (ρ = 0.85-0.98). DATA CONCLUSION: DTI of the pediatric physis cartilage shows high reproducibility between different imaging and analytic parameters. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Stressed or fractured: MRI differentiating indicators of physeal injury.

OBJECTIVE: To identify MRI findings that can indicate chronic physeal stress injury and differentiate it from acute Salter-Harris (SH) fracture of the pediatric knee or wrist. METHODS: IRB-approved retrospective study of consecutively selected knee and wrist MRIs from 32 athletes with chronic physeal stress injury and 30 children with acute SH fracture. MRI characteristics (physeal patency, physeal thickening, physeal signal intensity (SI), continuity of the zone of provisional calcification (ZPC), integrity of the periosteum and/or perichondrium, pattern of periphyseal and soft tissue edema signal, and joint effusion) were compared. RESULTS: Forty-eight chronic physeal stress injuries (mean age 13.1 years [8.2-17.5 years]) and 35 SH fractures (mean age 13.3 years [5.1-16.0 years]) were included. Any physeal thickening was more common with chronic stress injury (98% vs 77%, p = 0.003). Abnormal physeal SI was more common with SH fractures (91% vs 67%, p = 0.008). ZPC discontinuity strongly suggested chronic stress injury (79% vs 49%, p < 0.004). Periosteal and/or perichondrial elevation or rupture and soft tissue edema characterized most of the acute SH fractures (p < 0.001) and were seen only in 1 chronic stress injury (< 2%). While periphyseal edema was not significantly different in the two groups (p = 0.890), a joint effusion was associated with acute SH fracture (p < 0.001). CONCLUSION: Chronic physeal stress injury of the pediatric knee and wrist shows higher incidence of ZPC discontinuity and focal physeal thickening compared to SH fracture, reflecting disruption in normal endochondral ossification. However, these findings can overlap in the 2 groups. Periosteal and/or perichondrial injury, soft tissue edema signal, and joint effusion strongly suggest SH fracture and are rarely present with chronic stress injury.

Can diffusion tensor imaging unlock the secrets of the growth plate?

"How tall will I be?" Every paediatrician has been asked this during their career. The growth plate is the main site of longitudinal growth of the long bones. The chondrocytes in the growth plate have a columnar pattern detectable by diffusion tensor imaging (DTI). DTI shows the diffusion of water in a tissue and whether it is iso- or anisotropic. By detecting direction and magnitude of diffusion, DTI gives information about the microstructure of the tissue. DTI metrics include tract volume, length, and number, fractional anisotropy (FA), and mean diffusivity. DTI metrics, particularly tract volume, provide quantitative data regarding skeletal growth and, in conjunction with the fractional anisotropy, be used to determine whether a growth plate is normal. Tractography is a visual display of the diffusion, depicting its direction and amplitude. Tractography gives a more qualitative visualization of cellular orientation in a tissue and reflects the activity in the growth plate. These two components of DTI can be used to assess the growth plate without ionizing radiation or pain. Further refinements in DTI will improve prediction of post-imaging growth and growth plate closure, and assessment of the positive and negative effect of treatments like cis-retinoic acid and growth hormone administration.

The Influence of Temporary Epiphysiodesis of the Proximal End of the Tibia on the Shape of the Knee Joint in Children Treated for Leg Length Discrepancy.

Background: Leg length discrepancy (LLD) is a common problem in the daily clinical practice of pediatric orthopedists. Surgical treatment using LLD temporary epiphysiodesis with eight-plate implants is a minimally invasive, safe, and well-tolerated procedure that provides good treatment effects with a relatively low percentage of complications. The main aim of this retrospective study was to determine the effect of epiphysiodesis on the shape of the proximal tibia. Methods: The retrospective study was based on medical records from 2010 to 2019. Radiographs taken before the epiphysiodesis and at 6-month intervals until the end of the treatment were investigated. A total of 60 patients treated for LLD were included in the study (24 girls, 36 boys). They were divided into three groups depending on the duration of the LLD treatment: group I (18 months), group II (30 months), and group III (42 months of treatment). Radiological parameters were assessed, including the roof angle (D), the slope angles (α and ß), and the specific parameters of the tibial epiphysis, namely LTH (lateral tubercle height), MTH (medial tubercle height), and TW (tibial width). Results: The roof angle decreased in all the groups, which was accompanied by an increase in the ß or α angle. LTH, MTH and TW also increased, and the differences before and after the treatment for the treated legs were statistically significant in all the studied groups. The greatest change in the shape of the articular surface of the proximal tibia occurred after 42 months of treatment. Conclusions: The study showed that epiphysiodesis affects the proximal tibial articular surface over prolonged treatment. Thus, there is a need for future long-term follow-up studies to elucidate the potential effects of LLD egalization.

Lost in research translation: Female athletes are not male athletes, especially at the hip.

Altered shape of the proximal femur (cam morphology) or acetabulum (pincer morphology) is indicative of femoroacetabular impingement, which can result in hip pain and osteoarthritis of the hip. As mechanical load during growth affects the resulting bone shape, there is strong evidence in males that cam morphology develops during skeletal growth while physes are open, rather than as an adaptation after growth plates are closed (skeletal maturity). This adaptation is particularly evident in athletes who participate at elite levels prior to skeletal maturity. The research providing this evidence, however, has primarily focused on male athletes. Despite the lack of inclusion in the research, females consistently comprise two thirds of the clinical and surgical populations with structural hip pain or pathology. Knowledge gained from male-dominated cohorts may not appropriately transfer to female athletes, especially at the hip. This perspectives article briefly reviews differences between females and males in femoral and acetabular structure, hormones, timing of puberty/maturation, hypermobility, activity level and movement control-factors which affect hip structure development and loading. Without female-focused research, the application of research findings from male athletes to female athletes may lead to ineffective or even inappropriate recommendations and treatments. Thus, there is a critical need for investment in research to promote life-long hip health for females.

Specialist learning curves and clinical feasibility of introducing a new MRI grading system for skeletal maturity.

Objective: MRI is an emerging imaging modality to assess skeletal maturity. This study aimed to chart the learning curves of paediatric radiologists when using an unfamiliar MRI grading system of skeletal maturity and to assess the clinical feasibility of implementing said system. Methods: 958 healthy paediatric volunteers were prospectively included in a dual-facility study. Each subject underwent a conventional MRI scan at 1.5 T. To perform the image reading, the participants were grouped into five subsets (subsets 1-5) of equal size (n∼192) in chronological order for scan acquisition. Two paediatric radiologists (R1-2) with different levels of MRI experience, both of whom were previously unfamiliar with the study's MRI grading system, independently evaluated the subsets to assess skeletal maturity in five different growth plate locations. Congruent cases at blinded reading established the consensus reading. For discrepant cases, the consensus reading was obtained through an unblinded reading by a third paediatric radiologist (R3), also unfamiliar with the MRI grading system. Further, R1 performed a second blinded image reading for all included subjects with a memory wash-out of 180 days. Weighted Cohen kappa was used to assess interreader reliability (R1 vs consensus; R2 vs consensus) at non-cumulative and cumulative time points, as well as interreader (R1 vs R2) and intrareader (R1 vs R1) reliability at non-cumulative time points. Results: Mean weighted Cohen kappa values for each pair of blinded readers compared to consensus reading (interreader reliability, R1-2 vs consensus) were ≥0.85, showing a strong to almost perfect interreader agreement at both non-cumulative and cumulative time points and in all growth plate locations. Weighted Cohen kappa values for interreader (R1 vs R2) and intrareader reliability (R1 vs R1) were ≥0.72 at non-cumulative time points, with values ≥0.82 at subset 5. Conclusions: Paediatric radiologists' clinical confidence when introduced to a new MRI grading system for skeletal maturity was high from the outset of their learning curve, despite the radiologists' varying levels of work experience with MRI assessment. The MRI grading system for skeletal maturity investigated in this study is a robust clinical method when used by paediatric radiologists and can be used in clinical practice. Advances in knowledge: Radiologists with fellowship training in paediatric radiology experienced no learning curve progress when introduced to a new MRI grading system for skeletal maturity and achieved desirable agreement from the first time point of the learning curve. The robustness of the investigated MRI grading system was not affected by the earlier different levels of MRI experience among the readers.

Age-related changes in densitometry and histomorphometry of long bone during the pubertal growth spurt in male rats.

Because experimental studies to determine the developmental toxicity of exposure to various substances in children are impossible, many studies use immature male rats. This study aimed to provide normative data for longitudinal bone growth with age during the puberty in male rats. In order to evaluate long bone growth and mineralization we examined bone size and bone density by dual-energy X-ray absorptiometry, analyzed histomorphometry of the growth plate, and serum hormone levels relevant to bone growth from postnatal day (PD)20 to PD60. The length and weight of long bones increased strongly by PD40, and no further increase was observed after PD50. On the other hand, tibial growth plate height decreased sharply after PD50 along with a reduction in the number of cells and columns, which was probably responsible for the absence of further lengthening of long bones. Parameters related to bone formation such as bone area ratio, and the thickness and number of trabeculae, also increased significantly between PD40 and PD50. Furthermore, serum levels of IGF-1 peaked at PD30 and testosterone increased rapidly on and after PD40, when IGF-1 levels were going down. These changes may participate in the parallel increase in mineral acquisition, as well as lengthening of long bones. Our findings provide comprehensive data for changes in bone density, histomorphometry of long bones, and hormone levels relevant to bone growth during the growth spurt. This will be useful for planning animal toxicological studies, particularly for deciding on the appropriate age of animals to use in given experiments.

OSTEOCHONDRITIS DISSECANS OF THE HIP IN LEGG-CALVÉ-PERTHES DISEASE: CASE REPORT AND REVIEW.

Introduction: Legg-Calvé-Perthes disease (LCPD) is the idiopathic osteonecrosis of the capital femoral epiphysis in children. It is a self-healing condition, and the morphology of the hip may vary according to the severity of the disease, among several other factors. The treatment focuses on attempts to prevent femoral head collapse, obtain functional hip motion recovery, and reduce pain. Osteochondritis Dissecans (OCD) of the femoral head has been reported in 2% to 7% of patients diagnosed with healed LCPD. Although OCD may remain asymptomatic, the osteochondral fragment has the potential to become unstable, evolving into symptoms of pain, locking, catching, and snapping. Case report: We present a case report of a ten-year-old boy with an OCD lesion following LCPD who underwent effective osteochondral fixation through the surgical hip dislocation approach. The patient evolved to excellent functional recovery at 1 year post-operatively. Discussion: The surgical hip dislocation approach allows anatomical fixation of the OCD fragment, as well as improvement of hip biomechanics, decreasing pain, improving range of motion and joint congruency, and preserving the native articular cartilage. It also gives the surgeon the opportunity to assess hip stability, femoroacetabular impingement and labral tears, allowing a wide variety of options for the treatment of the healed LCPD. Level of Evidence IV; Type of study Case Report.

Introdução: A Doença de Legg-Calvé-Perthes (DLCP) é a osteonecrose idiopática da epífise femoral proximal em crianças. É uma condição auto resolutiva, porém a morfologia final do quadril pode variar de acordo com a gravidade da doença. O tratamento concentra-se na tentativa de prevenir o colapso da cabeça femoral, obtendo recuperação funcional do movimento do quadril e redução da dor. A osteocondrite dissecante (OCD) da cabeça femoral foi relatada em 2% a 7% dos pacientes diagnosticados com DLCP já curada. Embora a OCD possa permanecer assintomática, o fragmento osteocondral tem potencial para se tornar instável, evoluindo para sintomas de dor, bloqueio, impacto e estalido. Relato de caso: Apresentamos o relato de caso de um menino de 10 anos com OCD da cabeça femoral após DLCP, submetido à fixação osteocondral do fragmento por meio da abordagem cirúrgica de luxação do quadril. O paciente evoluiu com excelente recuperação funcional 1 ano após a cirurgia. Discussão: A abordagem cirúrgica da luxação do quadril permite a fixação anatômica do fragmento da OCD, bem como a melhora da biomecânica do quadril, diminuindo a dor, melhorando a amplitude de movimento e a congruência articular e preservando a cartilagem articular nativa. Também dá ao cirurgião a oportunidade de avaliar a estabilidade do quadril, impacto femoroacetabular e lesões labrais, permitindo uma ampla variedade de opções para o tratamento das sequelas da DLCP. Nível de evidência IV; tipo de estudo Relato de Casos.

Depletion of SMN protein in mesenchymal progenitors impairs the development of bone and neuromuscular junction in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cell (MPC)-specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ). Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor (IGF) signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors (FAPs) resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.

Regulatory Pathways in Growth Plate Chondrocytes that Are Impacted by Matrix Vesicle microRNA Identified by Targeted RISC Pulldown and Sequencing of the Resulting Transcriptome.

During endochondral bone formation, growth plate chondrocytes are differentially regulated by various factors and hormones. As the cellular phenotype changes, the composition of the extracellular matrix is altered, including the production and composition of matrix vesicles (MV) and their cargo of microRNA. The regulatory functions of these MV microRNA in the growth plate are still largely unknown. To address this question, we undertook a targeted bioinformatics approach. A subset of five MV microRNA was selected for analysis based on their specific enrichment in these extracellular vesicles compared to the parent cells (miR-1-3p, miR-22-3p, miR-30c-5p, miR-122-5p, and miR-133a-3p). Synthetic biotinylated versions of the microRNA were produced using locked nucleic acid (LNA) and were transfected into rat growth plate chondrocytes. The resulting LNA to mRNA complexes were pulled down and sequenced, and the transcriptomic data were used to run pathway analysis pipelines. Bone and musculoskeletal pathways were discovered to be regulated by the specific microRNA, notably those associated with transforming growth factor beta (TGFß) and Wnt pathways, cell differentiation and proliferation, and regulation of vesicles and calcium transport. These results can help with understanding the maturation of the growth plate and the regulatory role of microRNA in MV.

Chondrocyte hypertrophy in the growth plate promotes stress anisotropy affecting long bone development through chondrocyte column formation.

The length of long bones is determined by column formation of proliferative chondrocytes and subsequent chondrocyte hypertrophy in the growth plate during bone development. Despite the importance of mechanical loading in long bone development, the mechanical conditions of the cells within the growth plate, such as the stress field, remain unclear owing to the difficulty in investigating spatiotemporal changes within dynamically growing tissues. In this study, the mechanisms of longitudinal bone growth were investigated from a mechanical perspective through column formation of proliferative chondrocytes within the growth plate before secondary ossification center formation using continuum-based particle models (CbPMs). A one-factor model, which simply describes essential aspects of a biological signaling cascade regulating cell activities within the growth plate, was developed and incorporated into CbPM. Subsequently, the developmental process and maintenance of the growth plate structure and resulting bone morphogenesis were simulated. Thus, stress anisotropy in the proliferative zone that affects bone elongation through chondrocyte column formation was identified and found to be promoted by chondrocyte hypertrophy. These results provide further insights into the mechanical regulation of multicellular dynamics during bone development.