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It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4-week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones. Lastly, microCT analysis revealed no difference between loaded and unloaded tibiae with respect to the fraction of bone volume relative to the total volume of the region of interest or the tibial trabecular bone volume. Thus, our findings suggest that intermittent compressive forces applied on tibiae at mild-moderate strain magnitude induce a significant and persistent longitudinal bone growth. PTHrP expressed in the growth plate appears to be one growth factor responsible for stimulating endochondral ossification and bone growth in female mice.
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Placa de Crecimiento , Proteína Relacionada con la Hormona Paratiroidea , Tibia , Soporte de Peso , Animales , Femenino , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Proteína Relacionada con la Hormona Paratiroidea/genética , Tibia/metabolismo , Tibia/crecimiento & desarrollo , Tibia/diagnóstico por imagen , Placa de Crecimiento/metabolismo , Placa de Crecimiento/crecimiento & desarrollo , Ratones , Soporte de Peso/fisiología , Estrés Mecánico , Ratones Endogámicos C57BL , Desarrollo Óseo , Osteogénesis/fisiologíaRESUMEN
Tartrate-resistant acid phosphatase (TRAP) serum levels reflect osteoclast number, bone remodeling activity, and fracture risk. Deletion or loss of function of TRAP results in short stature in mice and man. Yet, the impact and mechanisms of TRAP for the site- and sex-specific development of bone and cartilage is not well understood. Here, we use a global TRAP knockout (TRAPKO) and wildtype littermate control (WT) mice of both sexes to investigate TRAP as a possible sex- and site-specific regulator of bone and growth plate development. TRAPKO mice of both sexes weighed less and had shorter tibial length than their WT, features that were more accentuated in male than female TRAPKO mice. These changes were not associated with a general reduction in growth as not all organs displayed a proportionally lower mass, and serum IGF-1 was unchanged. Using µCT and site-specificity analysis of the cortical bone revealed wider proximal tibia, a higher trabecular thickness, and lower trabecular separation in male TRAPKO compared to WT mice, an effect not seen in female mice. Histomorphometric analysis revealed that the growth plate height as well as height of terminal hypertrophic chondrocytes were markedly increased, and the number of columns was decreased in TRAPKO mice of both sexes. These effects were more accentuated in female mice. Proliferation and differentiation of bone marrow derived macrophages into osteoclasts, as well as C-terminal cross links were normal in TRAPKO mice of both sexes. Collectively, our results show that TRAP regulates bone and cartilage development in a sex-and site-specific manner in mice.
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Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive. To address these aspects, we have generated conditional knockout mouse models targeting the cellular FN isoform in cartilage (cFNKO), the plasma FN isoform in hepatocytes (pFNKO), and both isoforms together in a double knockout (FNdKO). We used these mice to determine the relevance of the two principal FN isoforms in skeletal development from P1 to the adult stage at two months. We identified a distinct topological FN deposition pattern in the mouse limb during different gestational and postnatal skeletal development phases, with prominent levels at the resting and hypertrophic chondrocyte zones and in the trabecular bone. Cartilage-specific cFN emerged as the predominant isoform in the growth plate, whereas circulating pFN remained excluded from the growth plate and confined to the primary and secondary ossification centers. Deleting either isoform independently (cFNKO or pFNKO) yielded only relatively subtle changes in the analyzed skeletal parameters. However, the double knockout of cFN in the growth plate and pFN in the circulation of the FNdKO mice significantly reduced postnatal body weight, body length, and bone length. Micro-CT analysis of the adult bone microarchitecture in FNdKO mice exposed substantial reductions in trabecular bone parameters and bone mineral density. The mice also showed elevated bone marrow adiposity. Analysis of chondrogenesis in FNdKO mice demonstrated changes in the resting, proliferating and hypertrophic growth plate zones, consistent alterations in chondrogenic markers such as collagen type II and X, decreased apoptosis of hypertrophic chondrocytes, and downregulation of bone formation markers. Transforming growth factor-ß1 and downstream phospho-AKT levels were significantly lower in the FNdKO than in the control mice, revealing a crucial FN-mediated regulatory pathway in chondrogenesis and bone formation. In conclusion, the data demonstrate that FN is essential for chondrogenesis and bone development. Even though cFN and pFN act in different regions of the bone, both FN isoforms are required for the regulation of chondrogenesis, cartilage maturation, trabecular bone formation, and overall skeletal growth.
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T-2 toxin, the most toxic type A trichothecene, is widely present in grain and animal feed, causing growth retardation and tissue damage in poultry. Geese are more sensitive to T-2 toxin than chickens and ducks. Although T-2 toxin has been reported to cause tibial growth plate (TGP) chondrodysplasia in chickens, tibial damage caused by T-2 toxin in geese has not been fully demonstrated. This study aims to investigate the adverse effects of T-2 toxin on tibial bone development, bone quality, chondrocyte differentiation, and bone metabolism. Here, forty-eight one-day-old male Yangzhou goslings were randomly divided into four groups and daily gavaged with T-2 toxin at concentrations of 0, 0.5, 1.0, and 2.0 mg/kg body weight for 21 days, respectively. The development of gosling body weight and size was determined by weighing and taking body measurements after exposure to different concentrations of T-2 toxin. Changes in tibial development and bone characteristics were determined by radiographic examination, phenotypic measurements, and bone quality and composition analyses. Chondrocyte differentiation in TGP and bone metabolism was characterized by cell morphology, tissue gene-specific expression, and serum marker levels. Results showed that T-2 toxin treatment resulted in a lower weight, volume, length, middle width, and middle circumference of the tibia in a dose-dependent manner (p < 0.05). Moreover, decreased bone-breaking strength, bone mineral density, and contents of ash, Ca, and P in the tibia were observed in T-2 toxin-challenged goslings (p < 0.05). In addition, T-2 toxin not only reduced TGP height (p < 0.05) but also induced TGP chondrocytes to be disorganized with reduced numbers and indistinct borders. As expected, the apoptosis-related genes (CASP9 and CASP3) were significantly up-regulated in chondrocytes challenged by T-2 toxin with a dose dependence, while cell differentiation and maturation-related genes (BMP6, BMP7, SOX9, and RUNX2) were down-regulated (p < 0.05). Considering bone metabolism, T-2 toxin dose-dependently and significantly induced a decreased number of osteoblasts and an increased number of osteoclasts in the tibia, with inhibited patterns of osteogenesis-related genes and enzymes and increased patterns of osteoclast-related genes and enzymes (p < 0.05). Similarly, the serum Ca and P concentrations and parathyroid hormone, calcitonin, and 1, 25-dihydroxycholecalciferol levels decreased under T-2 toxin exposure (p < 0.05). In summary, 2.0 mg/kg T-2 toxin significantly inhibited tibia weight, length, width, and circumference, as well as decreased bone-breaking strength, density, and composition (ash, calcium, and phosphorus) in 21-day-old goslings compared to the control and lower dose groups. Chondrocyte differentiation in TGP was delayed by 2.0 mg/kg T-2 toxin owing to cell apoptosis. In addition, 2.0 mg/kg T-2 toxin promoted bone resorption and inhibited osteogenesis in cellular morphology, gene expression, and hormonal modulation patterns. Thus, T-2 toxin significantly inhibited tibial growth and development with a dose dependence, accompanied by decreased bone geometry parameters and properties, hindered chondrocyte differentiation, and imbalanced bone metabolism.
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Tibial dyschondroplasia (TD) is a severe bone disease that affects fast-growing broiler chickens and causes economic loss. Despite previous studies, the regulatory mechanism of TD remains unclear and is thought to be primarily based on thiram induction, which may differ from that of naturally occurring diseases. To better understand TD, a digital X-ray machine was used in the present study to determine its incidence in four hundred yellow-feathered broiler chickens. The results showed that the incidence of TD was 22% after 6 weeks and gradually decreased after 8 and 10 weeks. The body weight of broilers with TD decreased significantly compared to that of NTD broilers. In addition, the length and density of the tibia were reduced after eight and 10 weeks, and the density of the tibia was reduced after 6 weeks compared with the NTD chickens. This study also examined tibial quality parameters from TD (n = 12) and NTD broilers (n = 12) and found that bone mineral content, bone mineral density, bone ash content, calcium content, and phosphorus content were significantly reduced in TD broilers. Transcriptome analysis revealed 849 differentially expressed genes (DEGs) in the growth plate between TD (n = 6) and NTD groups (n = 6). These genes were enriched in ECM-receptor interaction, cytokine-cytokine receptor interaction, calcium signaling pathway, and TGF-ß signaling. Genes encoding the alpha chain of type XII collagen, that is, COL1A1, COL5A1, and COL8A1) were identified as critical in the regulatory network of TD. Gene set enrichment analysis (GSEA) revealed that the pathways of cartilage development, circulatory system development, and nervous system development were changed in the growth plates of TD birds. In the blood transcriptome, 12 DEGs were found in TD (n = 4) and NTD chickens (n = 4), and GSEA revealed that the pathways from TD broilers' blood related to the phagosome, linoleic acid metabolism, monoatomic ion homeostasis, and calcium ion transport were downregulated. This study provides a comprehensive understanding of TD, including its effects on tibial quality, tibial changes, and the circulatory system, along with identifying important genes that may lead to the development of TD.
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Ankyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome.
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Fenotipo , Proteínas Represoras , Humanos , Proteínas Represoras/genética , Anomalías Múltiples/genética , Discapacidad Intelectual/genética , Anomalías Dentarias/genética , Anomalías Dentarias/patología , Craneosinostosis/genética , Craneosinostosis/patología , Deleción Cromosómica , Enfermedades del Desarrollo Óseo , FaciesRESUMEN
The growth plate is a cartilage structure at the end of long bones which mediates growth in children. When fractured, the formation of bony repair tissue known as a "bony bar" can occur and cause limb deformities. There are currently no effective clinical solutions for the prevention of the bony bar formation or regeneration of healthy growth plate cartilage after a fracture. This study employs previously developed alginate/chitosan polyelectrolyte complex (PEC) hydrogels as a sustained release vehicle for the delivery of short-interfering RNA (siRNA). Specifically, the siRNA targets the p38-MAPK pathway in mesenchymal stem cells (MSCs) to prevent their osteogenic differentiation. In vitro experimental findings show sustained release of siRNA from the hydrogels for 6 months. Flow cytometry and confocal imaging indicate that the hydrogels release siRNA to effectively knockdown GFP expression over a sustained period. MAPK-14 targeting siRNA was used to knockdown the expression of MAPK-14 and correspondingly decrease the expression of other osteogenic genes in MSCs in vitro over the span of 21 days. These hydrogels were used in a rat model of growth plate injury to determine whether siMAPK-14 released from the gels could inhibit bony bar formation. No significant reduction of bony bar formation was seen in vivo at the one concentration of siRNA examined. This PEC hydrogel represents a significant advancement for siRNA sustained delivery, and presents an interesting potential therapeutic delivery system for growth plate injuries and other regenerative medicine applications.
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Background: The proximal tibial epiphyseal inclination can be used as a prognostic factor for good results after knee osteotomy and measured using the tibial bone varus angle (TBVA). This angle depends on the visibility of the epiphyseal plate, which has shown poor reproducibility when measured on standard radiographs by conventional methods. Purpose: To evaluate the measurement reliability of the TBVA and other angles based on the epiphyseal scar using a digital image display. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 100 whole-leg radiographs were analyzed twice by 3 orthopaedic surgeons from 2 countries in a blinded and randomized manner. Observers measured the hip-knee-ankle angle, mechanical lateral distal femoral angle, medial proximal tibial angle, and TBVA. The growth plate-tibial plateau (GPTP) angle, defined as the angle between the epiphyseal scar and tibial plateau, was measured; this angle has not yet been described for osteotomy. In addition, a modified version of the TBVA (mTBVA), defined as that between the epiphyseal scar, its center, and the center of the talus, was measured. The Ahlbäck score for osteoarthritis and a 3-grade score for epiphyseal scar visibility were also determined. The reliability of the angle measurements and scoring was evaluated using the Fleiss kappa and intraclass correlation coefficient (ICC). Results: The scores for epiphyseal scar visibility showed fair interobserver (Fleiss kappa correlation coefficient [κ] = 0.29-0.35) and strong intraobserver (Fleiss κ = 0.62-0.69) reliability. TBVA, GPTP angle, and mTBVA measurements showed good interobserver reliability (ICC, 0.76-0.77), while the GPTP angle achieved excellent intraobserver reliability (ICC, >0.9). Conclusion: Using digital image display, angles that depend on the epiphyseal scar-such as TBVA, GPTP angle, and mTBVA-can achieve acceptable measurement reliability despite the low agreement on the visibility of the epiphyseal scar.
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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.
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Cartílago , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Selenoproteínas , Animales , Selenoproteínas/metabolismo , Selenoproteínas/genética , Ratones , Cartílago/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Condrocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea CelularRESUMEN
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.
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This study aimed to assess the fusion of growth plates and the development of secondary ossification centres in the forelimb bones of maned wolves (Chrysocyon brachyurus), contrasting the findings with established data from domestic dogs. Three maned wolves, comprising one male and two females, initially aged between 3 and 4 months, were subjected to monthly radiographic evaluations until 10-11 months of age, followed by bimonthly assessments until 18-19 months of age, encompassing both forelimbs. The closure times of growth plates were observed as follows: supraglenoid tubercle (7-8 months), proximal humerus (17-19 months), distal humerus (8-9 months), medial epicondyle of the humerus (8-9 months), proximal ulna (9-10 months), proximal radius (13-15 months), distal ulna (13-15 months) and distal radius (17-19 months). Statistical analysis revealed significant differences in the areas of secondary ossification centres in the proximal epiphyses of the humerus and radius, respectively, observed from the initial evaluation at 8-9 months and 6-7 months. Conversely, the epiphyses of the supraglenoid tubercle, distal humerus, proximal ulna, distal ulna, medial epicondyle of the humerus and distal radius did not exhibit significant area differences between 3-4 months and 4-5 months, yet notable distinctions emerged at 5-6 months. In summary, while the radiographic appearance of epiphyseal growth plates and secondary ossification centres in maned wolves resembles that of domestic dogs, closure times vary. These findings contribute to understanding the dynamics of epiphyseal growth plates in this species.
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Desarrollo Óseo , Canidae , Miembro Anterior , Húmero , Radio (Anatomía) , Cúbito , Animales , Miembro Anterior/anatomía & histología , Miembro Anterior/diagnóstico por imagen , Masculino , Femenino , Canidae/anatomía & histología , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/anatomía & histología , Radio (Anatomía)/crecimiento & desarrollo , Cúbito/diagnóstico por imagen , Cúbito/anatomía & histología , Cúbito/crecimiento & desarrollo , Desarrollo Óseo/fisiología , Húmero/anatomía & histología , Húmero/diagnóstico por imagen , Húmero/crecimiento & desarrollo , Placa de Crecimiento/diagnóstico por imagen , Placa de Crecimiento/anatomía & histología , Placa de Crecimiento/crecimiento & desarrollo , Radiografía/veterinaria , Osteogénesis/fisiología , Perros/anatomía & histología , Perros/crecimiento & desarrolloRESUMEN
BACKGROUND: There is no consensus on the treatment of juvenile hallux valgus (JHV). Numerous surgical techniques have been described, none of which has been proven to be superior and the mid-term results of these methods are not well known. Our objective was to compare the mid-term clinical, radiographic, and functional results of three metatarsal osteotomy techniques. METHODS: Patients under 18 years of age operated on for JHV between January 2010 and December 2019 were included in this multicenter retrospective study. Patients were excluded if they had non-idiopathic hallux valgus or if their postoperative follow-up was less than 3 years. The surgical techniques used were metatarsal osteotomies: basimetatarsal, scarf, or distal. During follow-up visits, we collected HMIS-AOFAS (Hallux Metatarsophalangeal Interphalangeal Scale-American Orthopedic Foot and Ankle Society) and Visual Analogue Scale (VAS) scores, acquired radiographs, and recorded complications and recurrences. Secondarily, the study population was stratified according to physis status (open vs. closed). RESULTS: During the study period, 18 patients (26 feet) met the inclusion criteria. The median postoperative follow-up was 6.5 (4.1) years. At the end of follow-up, the median HMIS score was 79.0 (20.0), the mean hallux valgus angle (HVA) improvement was 13.2° (16.8), and the complication and recurrence rates were 31 % and 23 %, respectively. There was no significant difference in the outcome measures between the three techniques or any difference according to physis status at the time of surgery. DISCUSSION AND CONCLUSION: The functional and radiographic results of metatarsal osteotomies are good in the medium term, regardless of the osteotomy site. Our results are comparable to those published in the literature. As our sample size was limited, it did not lead to the identification of statistically significant differences.
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Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of the quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological centre of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the keywords: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and "Turner syndrome"; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its aetiology. The angular and linear cephalometric measurements differ from the measurements of the average normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusions: The greater part of the existing literature regarding cephalometric measurements in short-statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature should be the focus of future studies. These quantitative data are required to potentially establish cut-off values for reference for genetic testing based on craniofacial phenotypes.
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INTRODUCTION: Growth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair. METHODS: Chondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT. RESULTS: Glycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks. CONCLUSION: This study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.
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Condrocitos , Gangliósidos , Placa de Crecimiento , Ratones Endogámicos C57BL , Ratones Noqueados , Animales , Placa de Crecimiento/patología , Placa de Crecimiento/metabolismo , Gangliósidos/metabolismo , Condrocitos/metabolismo , Ratones , Diferencia de Longitud de las Piernas , Tibia/diagnóstico por imagen , Tibia/patología , Tibia/metabolismo , Tibia/crecimiento & desarrollo , Microtomografía por Rayos X , Sialiltransferasas/deficiencia , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Modelos Animales de EnfermedadRESUMEN
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.
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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.
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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.
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Traumatismos de los Pies , Humanos , Niño , Traumatismos de los Pies/terapia , Traumatismos del Tobillo/terapia , Traumatismos del Tobillo/diagnóstico , Traumatismos del Tobillo/cirugía , Adolescente , Preescolar , Lactante , Fracturas Óseas/terapiaRESUMEN
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.
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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.
Asunto(s)
Recién Nacido Pequeño para la Edad Gestacional , Humanos , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Recién Nacido , Niño , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Desarrollo Infantil/fisiologíaRESUMEN
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.