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BACKGROUND: Meniscal repair should be the gold standard. However, the meniscus is poorly vascularized and even an excellent meniscus repair may not heal. Therefore, numerous studies and systematic reviews have been carried out on platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and fibrin clots for meniscal augmentation, but the results remain controversial. This systematic review aimed to identify other emerging strategies for meniscal repair augmentation and to assess whether there are different avenues to explore in this field. METHODS: A systematic literature review was conducted in August 2022. PubMed, Ovid MEDLINE(R) all, Ovid All EBM Reviews, Ovid Embase and ISI Web of Science databases were searched. In Vivo animal and human studies concerning the biological augmentation of meniscal lesions by factors other than PRP, MSCs or fibrin clots were included. Cartilage-only studies, previous systematic reviews and expert opinions were excluded. All data were analyzed by two independent reviewers. RESULTS: Of 8965 studies only nineteen studies covering 12 different factors met the inclusion criteria. Eight studies investigated the use of growth factors for meniscal biologic augmentation, such as vascular endothelial growth factor or bone morphogenic protein 7. Five studies reported on cell therapy and six studies focused on other factors such as hyaluronic acid, simvastatin or atelocollagen. Most studies (n = 18) were performed on animal models with gross observation and histological evaluation as outcomes. Polymerase chain reaction and immunohistochemistry were also common. Biomechanical testing was the object of only two studies. CONCLUSIONS: Although several augmentation strategies have been attempted, none has yielded conclusive results, testifying to a lack of understanding with regard to meniscal healing. More research is needed to better understand the pathways that regulate meniscus repair and how to act positively on them. LEVEL OF EVIDENCE: Systematic review of case-control and animal laboratory studies.
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Lesões do Menisco Tibial , Humanos , Lesões do Menisco Tibial/cirurgia , Lesões do Menisco Tibial/terapia , Animais , Meniscos Tibiais/cirurgia , Cicatrização/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this study, we investigated the effects of two functionalized nanogels as DDS. We assessed the effect of chitosan functionalized with a type A endothelin receptor antagonist (BQ-123-CHI) and/or hyaluronic acid functionalized with a type B1 bradykinin receptor antagonist (R-954-HA). The biocompatibility of these nanogels, alone or in combination, was first validated on equine articular chondrocytes cultured under different oxic conditions. Further, in an OA equine organoid model via induction with interleukin-1 beta (IL-1ß), a combination of BQ-123-CHI and R-954-HA (BR5) triggered the greatest decrease in inflammatory and catabolic markers. In basal and OA conditions, BQ-123-CHI alone or in equimolar combinations with R-954-HA had weak pro-anabolic effects on collagens synthesis. These new nanogels, as part of a composite DDS, show promising attributes for treating OA.
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Cartilagem Articular , Osteoartrite , Animais , Antagonistas dos Receptores da Bradicinina/metabolismo , Antagonistas dos Receptores da Bradicinina/farmacologia , Antagonistas dos Receptores da Bradicinina/uso terapêutico , Cartilagem/metabolismo , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Endotelina-1/metabolismo , Cavalos , Humanos , Interleucina-1beta/metabolismo , Nanogéis , Organoides/metabolismo , Osteoartrite/metabolismoRESUMO
INTRODUCTION: Vitamin D (VitD) maintains bone health and may influence orthodontic tooth movement (OTM). The objective was to evaluate the VitD effect on bone morphometry and the rate and stability of OTM. METHODS: Thirty-two male Sprague Dawley rats were assigned into 2 experimental groups, treated with VitD by gavage (systemic) or injection (local), and 2 respective control groups treated with phosphate-buffered saline for 47 days. OTM was performed for 7 days with a nickel-titanium coil bonded between the maxillary first molar and incisors. Microcomputed tomography scanning was performed at 5 time points: before administration of VitD, the start of OTM, the end of OTM, 7 days post-OTM, and 30 days post-OTM. The rate and stability of OTM were assessed. Bone morphometry was analyzed by bone mineral density, bone volume/total volume, total porosity, trabecular pattern factor, structure model index, and connectivity density. RESULTS: The systemic VitD group showed a lower OTM rate and a lower relapse than the control (P <0.05). It also demonstrated increased bone mineral density, bone volume/total volume, and a decrease in total porosity (P <0.05). The bone structure appeared more fragmented and presented a lower connectivity density than the control (P <0.05). No statistical difference was found between VitD local administration and the other groups for the rate and stability of OTM or bone morphometry. CONCLUSIONS: The systemic administration of VitD caused a decrease in the OTM rate by generating more bone resistance but also contributed to a lower relapse with a higher bone mineral density.
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Técnicas de Movimentação Dentária , Vitamina D , Ratos , Masculino , Animais , Técnicas de Movimentação Dentária/métodos , Microtomografia por Raio-X/métodos , Vitamina D/farmacologia , Ratos Sprague-Dawley , Recidiva , OsteoclastosRESUMO
The objective of this study was to investigate the effects of mechanical modulation parameters on structural proteins biocomposition and mechanical properties of the growth plate. Establishing these parameters is a crucial step in the development of fusionless treatment of scoliosis. In this study, ulna explants from 4-weeks-old (pubertal) swines were used. The biocomposition was characterized using biochemical content evaluation and immunohistochemistry. Mechanical properties were characterized by fitting the data of the stress relaxation curves using a fibril reinforced biphasic model. For the mechanical loading, one static modulation condition and three different dynamic modulation conditions, with similar average stress but different amplitude and frequency values, were performed using a bioreactor. Results showed that static loading triggers a decrease in proteoglycan content and type X collagen in specific zones of the growth plate. These changes can be associated with the observed decrement of permeability in the static group. None of the three conditions evaluated for dynamic modulation affected the growth plate biocomposition and biomechanical responses. Results of this study provides an improved understanding of growth plate responses to mechanical environment, which will be useful in finding the optimal and non-damaging parameters for fusionless treatments based on the mechanical modulation of bone growth.
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Matriz Extracelular/metabolismo , Lâmina de Crescimento/metabolismo , Ulna/metabolismo , Suporte de Carga/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Materiais Biomédicos e Odontológicos , Estresse Mecânico , SuínosRESUMO
This systematic review, registered with Prospero, aims to identify an optimal animal model for meniscus repair research, moving from ex vivo experimentation to in vivo studies. Data sources included PubMed, Medline, all Evidence-Based Medicine Reviews, Web of Science, and Embase searched in March 2023. Studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data including animal model, type of experiment, type of tear, surgical techniques, and measured outcomes, were recorded, reviewed, and analyzed by four independent reviewers. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) Rob tool was used for critical appraisal and risk of bias assessment. Out of 11,719 studies, 72 manuscripts were included for data extraction and analysis; 41 ex vivo extra-articular studies, 20 ex vivo intra-articular studies, and only 11 in vivo studies. Six animal models were employed: porcine, bovine, lapine, caprine, canine, and ovine. Longitudinal lesions were the most frequently studied tear pattern and sutures the most common repair technique. Studied outcomes focused mainly on biomechanical assessments and gross observations. This systematic review can guide researchers in their choice of animal model for meniscus repair research; it highlighted the strengths of the porcine, caprine, and bovine models for ex vivo cadaveric studies, while the porcine and caprine models were found to be more suited to in vivo studies due to their similarities with human anatomy. Research teams should familiarize themselves with the advantages and disadvantages of various animal models before initiating protocols to improve standardization in the field.
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Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.g., cartilage, eye, and contact lens), forming a robust, biocompatible layer for surface lubrication and protection. The tribological performance and biocompatibility are further enhanced in the presence of hyaluronic acid (HA) both in vitro and in vivo. The exceptional lubrication performance and favorable interaction with HA position the synthesized triblock polymer as a promising candidate for innovative treatments addressing deficiencies in bio-lubricant systems.
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Fricção , Ácido Hialurônico , Polímeros , Animais , Ácido Hialurônico/química , Polímeros/química , Polímeros/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Humanos , Lubrificação , Propriedades de Superfície , Lubrificantes/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologiaRESUMO
PURPOSE: Adolescent Idiopathic Scoliosis (AIS) is considered a complex genetic disease, in which malfunctioning or dysregulation of one or more genes has been proposed to be responsible for the expressed phenotype. However, to date, no disease causing genes has been identified and the pathogenesis of AIS remains unknown. The aim of this study is, therefore, to identify specific molecules with differing expression patterns in AIS compared to healthy individuals. METHODS: Microarray analysis and quantitative RT-PCR have examined differences in the gene transcription profile between primary osteoblasts derived from spinal vertebrae of AIS patients and those of healthy individuals. RESULTS: There are 145 genes differentially expressed in AIS osteoblasts. A drastic and significant change has been noted particularly in the expression levels of Homeobox genes (HOXB8, HOXB7, HOXA13, HOXA10), ZIC2, FAM101A, COMP and PITX1 in AIS compared to controls. Clustering analysis revealed the interaction of these genes in biological pathways crucial for bone development, in particular in the differentiation of skeletal elements and structural integrity of the vertebrae. CONCLUSIONS: This study reports on the expression of molecules that have not been described previously in AIS. We also provide for the first time gene interaction pathways in AIS pathogenesis. These genes are involved in various bone regulatory and developmental pathways and many of them can be grouped into clusters to participate in a particular biological pathway. Further studies can be built on our findings to further elucidate the association between different biological pathways and the pathogenesis of AIS.
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Perfilação da Expressão Gênica , Escoliose/genética , Adolescente , Criança , Análise por Conglomerados , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The burden of osteoarthritis (OA), one of the major causes of functional disabilities in humans and animals, continues to increase worldwide while no disease-modifying OA drugs (DMOADs) that either slow down or reverse disease progression have been made available. Here, we provide a brief overview of recent advances in: designing new OA drug delivery approaches, focusing on lubrication-based biomaterials and drug delivery systems, such as hydrogels, liposomes, dendrimers, micro- and nanoparticles; using either large (horse) or small (zebrafish) relevant animal models to evaluate new therapeutic strategies; and OA in vitro modeling, focusing on 3D (organoid) models of cartilage regarding the Replace, Reduce and Refine (3R) principle of animal experimentation.
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Osteoartrite , Peixe-Zebra , Humanos , Animais , Cavalos , Osteoartrite/tratamento farmacológico , Sistemas de Liberação de MedicamentosRESUMO
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 (POC5) was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify POC5 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the POC5 gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant POC5A429V AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of POC5, which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the POC5 promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.
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Proteínas de Transporte , Receptor alfa de Estrogênio , Escoliose , Humanos , Proteínas de Transporte/genética , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Escoliose/genética , Escoliose/metabolismoRESUMO
There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.
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Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.
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Nitric oxide (NO) and the lipid peroxidation (LPO) product 4-hydroxynonenal (HNE) are considered to be key mediators of cartilage destruction in osteoarthritis (OA). NO is also known to be an important intermediary in LPO initiation through peroxynitrite formation. The aim of the present study was to assess the ability of the inducible NO synthase (iNOS) inhibitor N-iminoethyl-L-lysine (L-NIL) to prevent HNE generation via NO suppression in human OA chondrocytes and cartilage explants. Human OA chondrocytes and cartilage explants were treated with L-NIL and thereafter with or without interleukin-1beta (IL-1ß) or HNE at cytotoxic or non-cytotoxic concentrations. Parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated. L-NIL stifled IL-1ß-induced NO release, iNOS activity, nitrated proteins, and HNE generation in a dose-dependent manner. It also blocked IL-1ß-induced inactivation of the HNE-metabolizing glutathione-s-transferase (GST). L-NIL restored both HNE and GSTA4-4 levels in OA cartilage explants. Interestingly, it also abolished IL-1ß-evoked reactive oxygen species (ROS) generation and p47 NADPH oxidase activation. Furthermore, L-NIL significantly attenuated cell death and markers of apoptosis elicited by exposure to a cytotoxic dose of HNE as well as the release of prostaglandin E(2) and metalloproteinase-13 induced by a non-cytotoxic dose of HNE. Altogether, our findings support a beneficial effect of L-NIL in OA by (i) preventing the LPO process and ROS production via NO-dependent and/or independent mechanisms and (ii) attenuating HNE-induced cell death and different mediators of cartilage damage.
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Condrócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lisina/análogos & derivados , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Osteoartrite/metabolismo , Aldeídos/metabolismo , Apoptose/efeitos dos fármacos , Células Cultivadas , Condrócitos/patologia , Dinoprostona/metabolismo , Glutationa Transferase/metabolismo , Humanos , Inflamação , Interleucina-1beta/farmacologia , Lisina/farmacologia , Metaloproteinase 13 da Matriz/metabolismo , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Osteoartrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: The purpose of this review is to elucidate the metabolic processes involved in the pathogenesis of adolescent idiopathic scoliosis (AIS) in light of research by the present authors as well as current literature. METHODS: Pathogenetic mechanisms involved in AIS were modeled as (a) a form of neuromuscular scoliosis (in conjunction with an adverse mechanical environment such as bipedality), in which hormonal and other chemical factors act as regulators of skeletal muscle tone and function; (b) as a consequence of an abnormality in growth of the spinal column (in conjunction with an adverse mechanical environment such as bipedality), in which hormones and other chemical factors act as regulators of growth; and (c) as a mechanical failure of one side of the vertebral column due to a defect in trabecular formation or mineralization (in conjunction with an adverse mechanical environment such as bipedality); in which hormonal and other chemical factors act as regulators of bone formation, mineralization and/or resorption. RESULTS AND CONCLUSION: Current evidence supporting these models individually or in combination is discussed.
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Modelos Biológicos , Escoliose/metabolismo , Adolescente , Animais , HumanosRESUMO
One important challenge in treating avascular-degraded cartilage is the development of new drugs for both pain management and joint preservation. Considerable efforts have been invested in developing nanosystems using biomaterials, such as chitosan, a widely used natural polymer exhibiting numerous advantages, i.e., non-toxic, biocompatible and biodegradable. However, even if chitosan is generally recognized as safe, the safety and biocompatibility of such nanomaterials must be addressed because of potential for greater interactions between nanomaterials and biological systems. Here, we developed chitosan-based nanogels as drug-delivery platforms and established an initial biological risk assessment for osteocartilaginous applications. We investigated the influence of synthesis parameters on the physicochemical characteristics of the resulting nanogels and their potential impact on the biocompatibility on all types of human osteocartilaginous cells. Monodisperse nanogels were synthesized with sizes ranging from 268 to 382 nm according to the acidic solution used (i.e., either citric or acetic acid) with overall positive charge surface. Our results demonstrated that purified chitosan-based nanogels neither affected cell proliferation nor induced nitric oxide production in vitro. However, nanogels were moderately genotoxic in a dose-dependent manner but did not significantly induce acute embryotoxicity in zebrafish embryos, up to 100 µgâmL-1. These encouraging results hold great promise for the intra-articular delivery of drugs or diagnostic agents for joint pathologies.
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Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.
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Ligação Genética , Escoliose , Coluna Vertebral , Adolescente , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Reino UnidoRESUMO
Adolescent idiopathic scoliosis (AIS) is a complex common disorder of multifactorial etiology defined by a deviation of the spine in three dimensions that affects approximately 2% to 4% of adolescents. Risk factors include other affected family members, suggesting a genetic component to the disease. The POC5 gene was identified as one of the first ciliary candidate genes for AIS, as three variants were identified in large families with multiple members affected with idiopathic scoliosis. To assess the prevalence of p.(A429V), p.(A446T), and p.(A455P) POC5 variants in patients with AIS, we used next-generation sequencing in our cohort of French-Canadian and British families and sporadic cases. Our study highlighted a prevalence of 13% for POC5 variants, 7.5% for p.(A429V), and 6.4% for p.(A446T). These results suggest a higher prevalence of the aforementioned POC5 coding variants in patients with AIS compared to the general population.
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Proteínas de Transporte/genética , Variação Genética , Escoliose/genética , Adolescente , Canadá , Proteínas de Transporte/classificação , Estudos de Coortes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linhagem , Prevalência , Fatores de Risco , Escoliose/epidemiologia , Sequenciamento do ExomaRESUMO
Idiopathic Scoliosis (IS) is a relatively common condition and is estimated to affect as many as 3 % of youth aged 10-17 years (in the United States an estimated approximately 1.4 million otherwise healthy individuals). A clear understanding of the etiology will better direct optimization of evaluation, treatments and therapies, especially early treatments with less invasive methods. A mechanistic explanation of factors combining to initiate and then cause progression of this common condition-- in otherwise healthy pre-teenage and teenage patients--will be discussed. A recent well-designed structured systematic review states that 'strong evidence is lacking for a consistent pattern of occurrence and any abnormality', in other words there is no strong evidence for 'other associated diagnoses' in IS. And so, certain important inherent factors of IS merit greater discussion. Inherent, or intrinsic factors include: a natural susceptibility to develop a lateral and rotational deformity in the immature rapidly growing erect human spine, inherent torsion associated at the induction of deformity, biomechanics related to curve progression, and anthropology/bipedal gait. We know more today about factors related to the condition and its etiology than we have previously. Across multiple disciplines, a mechanistic approach to understanding the etiopathogenesis of IS, allows a reasonable 'theory' for IS etiology and its progression. We will discuss these inherent intrinsic factors in order to further add to our understanding of the theoretical etiopathogenesis. A better understanding of the etiology (and progression) may better direct ways to optimize evaluation, treatments and therapies, especially early treatments with less invasive methods.
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Bone is a unique living tissue, which responds to the mechanical stimuli regularly imposed on it. Adolescence facilitates a favorable condition for the skeleton that enables the exercise to positively influence bone architecture and overall strength. However, it is still dubious for how long the skeletal benefits gained in adolescence is preserved at adulthood. The current study aims to use a rat model to investigate the effects of in vivo low- (LI), medium- (MI), and high- (HI) intensity cyclic loadings applied during puberty on longitudinal bone development, morphometry, and biomechanics during adolescence as well as at adulthood. Forty-two young (4-week-old) male rats were randomized into control, sham, LI, MI, and HI groups. After a 5 day/week for 8 weeks cyclic loading regime applied on the right tibia, loaded rats underwent a subsequent 41-week, normal cage activity period. Right tibias were removed at 52 weeks of age, and a comprehensive assessment was performed using µCT, mechanical testing, and finite element analysis. HI and MI groups exhibited reduced body weight and food intake at the end of the loading period compared with shams, but these effects disappeared afterward. HI cyclic loading increased BMD, bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular spacing after loading. All loading-induced benefits, except BMD, persisted until the end of the normal cage activity period. Moreover, HI loading induced enhanced bone area, periosteal perimeter, and moment of inertia, which remained up to the 52nd week. After the normal cage activity at adulthood, the HI group showed increased ultimate force and stress, stiffness, postyield displacement and energy, and toughness compared with the sham group. Overall, our findings suggest that even though both trabecular and cortical bone drifted through age-related changes during aging, HI cyclic loading performed during adolescence can render lifelong benefits in bone microstructure and biomechanics. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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Physical activity is beneficial for skeletal development. However, impact sports during adolescence, leading to bone growth retardation and/or bone quality improvement, remains unexplained. This study investigated the effects of in vivo low (LI), medium (MI), and high (HI) impact loadings applied during puberty on bone growth, morphometry and biomechanics using a rat model. 4-week old rats (n = 30) were divided into control, sham, LI, MI, and HI groups. The impact was applied on the right tibiae, 5 days/week for 8 weeks mimicking walking (450 µÎµ), uphill running (850 µÎµ) and jumping (1250 µÎµ) conditions. Trabecular and cortical parameters were determined by micro-CT, bone growth rate by calcein labeling and toluidine blue staining followed by histomorphometry. Bio-mechanical properties were evaluated from bending tests. HI group reduced rat body weight and food consumption compared to shams. Bone growth rate also decreased in MI and HI groups despite developing thicker hypertrophic and proliferative zone heights. HI group showed significant increment in bone mineral density, trabecular thickness, cortical and total surface area. Ultimate load and stiffness were also increased in MI and HI groups. We conclude that impact loading during adolescence reduces bone growth moderately but improves bone quality and biomechanics at the end of the growing period.
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Densidade Óssea , Desenvolvimento Ósseo/fisiologia , Lâmina de Crescimento/fisiologia , Condicionamento Físico Animal , Tíbia/crescimento & desenvolvimento , Animais , Fenômenos Biomecânicos , Peso Corporal , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The physiological role and the regulation of ADGRG7 are not yet elucidated. The functional involvement of this receptor was linked with different physiological process such as reduced body weight, gastrointestinal function and recently, a gene variant in ADGRG7 was observed in patients with adolescent idiopathic scoliosis. Here, we identify the ADGRG7 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that ADGRG7 expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. ADGRG7 promoter studies indicate the presence of an ERα response half site in close vicinity of a specificity protein 1 (SP1) binding site. Mutation of the SP1 site completely abrogated the response to E2, indicating its essential requirement. ChIP confirmed the binding of SP1 and ERα to the ADGRG7 promoter. Our results identify the ADGRG7 gene as an estrogen-responsive gene under the control of ERα and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of ADGRG7 This article has an associated First Person interview with the first author of the paper.