RESUMEN
Numerous studies have investigated the role of collagen type 1 α1 (COL1A1) polymorphisms in musculoskeletal soft tissue injuries (MSTIs), yielding conflicting results. This study was designed to synthesize existing evidence and clarify the relationship between COL1A1 polymorphisms and MSTI susceptibility. We conducted a comprehensive literature search using PubMed, Cochrane Library, Web of Science, EMBASE, and Wanfang databases. Associations were assessed using odds ratios (ORs) with 95% confidence intervals (95% CIs) across five genetic models. Subgroup analyses were performed based on ethnicity and injury type. Additionally, trial sequential analysis (TSA) was utilized to assess information size and statistical power. We analyzed a total of 16 articles from 358 retrieved studies, encompassing 2094 MSTI cases and 4105 controls. Our pooled data revealed that individuals with the TT genotype of the rs1800012 polymorphism had a significantly reduced risk of MSTIs (TT vs. GG, OR = 0.53, 95% CI 0.35-0.82, P = 0.004; TT vs. TG + GG, OR = 0.54, 95% CI 0.36-0.80, P = 0.002). Ethnicity-based stratification showed a significant association in Caucasians but not Asians. However, no significant association was observed between the rs1107946 polymorphism and MSTIs, regardless of ethnicity or injury type. TSA indicated that the sample sizes may have been insufficient to yield conclusive results. In conclusion, our study supports the protective effect of the TT genotype of the rs1800012 polymorphism against MSTIs, particularly among Caucasians. However, the rs1107946 polymorphism does not appear to influence MSTI susceptibility.
Asunto(s)
Cadena alfa 1 del Colágeno Tipo I , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Traumatismos de los Tejidos Blandos , Humanos , Traumatismos de los Tejidos Blandos/genética , Cadena alfa 1 del Colágeno Tipo I/genética , Colágeno Tipo I/genéticaRESUMEN
There is growing evidence of genetic contributions to tendon and ligament pathologies. Given the high incidence and severity of tendon and ligament injuries in elite rugby, we studied whether 13 gene polymorphisms previously associated with tendon/ligament injury were associated with elite athlete status. Participants from the RugbyGene project were 663 elite Caucasian male rugby athletes (RA) (mean (standard deviation) height 1.85 (0.07) m, mass 101 (12) kg, age 29 (7) yr), including 558 rugby union athletes (RU) and 105 rugby league athletes. Non-athletes (NA) were 909 Caucasian men and women (56% female; height 1.70 (0.10) m, mass 72 (13) kg, age 41 (23) yr). Genotypes were determined using TaqMan probes and groups compared using Χ2 and odds ratio (OR). COLGALT1 rs8090 AA genotype was more frequent in RA (27%) than NA (23%; P = 0.006). COL3A1 rs1800255 A allele was more frequent in RA (26%) than NA (23%) due to a greater frequency of GA genotype (39% vs 33%). For MIR608 rs4919510, RA had 1.7 times the odds of carrying the CC genotype compared to NA. MMP3 rs591058 TT genotype was less common in RA (25.1%) than NA (31.2%; P < 0.04). For NID1 rs4660148, RA had 1.6 times the odds of carrying the TT genotype compared to NA. It appears that elite rugby athletes have an inherited advantage that contributes to their elite status, possibly via resistance to soft tissue injury. These data may, in future, assist personalised management of injury risk amongst athletes.Highlights The elite rugby athletes we studied had differing genetic characteristics to non-athletes regarding genetic variants previously associated with soft-tissue injury risk.COLGALT1 rs8090, COL3A1 rs1800255, MIR608 rs4919510, MMP3 rs591058 and NID1 rs4660148 were all associated with elite status in rugby.We propose that elite rugby athletes might possess an inherited resistance to soft tissue injury, which has enabled them to achieve elite status despite exposure to the high-risk environment of elite rugby.
Asunto(s)
Fútbol Americano , MicroARNs , Traumatismos de los Tejidos Blandos , Humanos , Masculino , Femenino , Adulto , Metaloproteinasa 3 de la Matriz , Rugby , Alelos , Traumatismos de los Tejidos Blandos/genéticaRESUMEN
OBJECTIVE: Inconsistent findings existed on the correlation of collagen type V α1 (COL5A1) gene polymorphisms and musculoskeletal soft tissue injuries (MSTIs). The purpose of this study was to collect and combine the current evidences by a meta-analysis approach. METHODS: Six online databases were searched up to August, 2021. The methodological quality of each individual study was evaluated based upon Newcastle-Ottawa Scale (NOS). The strength of the effect size was presented by odds ratio (OR) with 95% confidence interval (95%CI) in five genetic models. The data were analyzed using Review Manager 5.3. RESULTS: Twenty-one studies were eligible to this meta-analysis. The study quality was deemed fair to excellent according to NOS. In the overall analyses, the merged data suggested that rs12722, rs71746744, and rs3196378 polymorphisms were correlated to an increased susceptibility to MSTIs. But the association was not established in rs13946 or rs11103544 polymorphism. For rs12722 polymorphism, stratified analyses by injury type and ethnicity identified the association mainly existed in ligament injury and among Caucasian population. For rs13946 polymorphism, subgroup analysis suggested the association existed in tendon and ligament injuries. CONCLUSION: This study supports that rs12722 is associated with an elevated susceptibility to ligament injury, especially in the Caucasian population. Rs13946 polymorphism appears to increase the risk to tendon and ligament injuries. Rs71746744 and rs3196378 polymorphisms have a tendency to confer an elevated risk to MSTIs. However, no relevance is found between rs11103544 polymorphism and MSTIs.
Asunto(s)
Colágeno Tipo V/genética , Sistema Musculoesquelético , Polimorfismo de Nucleótido Simple/genética , Traumatismos de los Tejidos Blandos/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Estudios Observacionales como Asunto , Población BlancaRESUMEN
The myotendinous junction (MTJ) is at high risk of muscle injury, and collagen XXII is strictly expressed at tissue junctions, specifically at the MTJ. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) related to collagen type XXII α-1 chain gene (COL22A1) mRNA expression are associated with susceptibility to muscle injury in athletes. History of muscle injury was assessed in 3,320 Japanese athletes using a questionnaire, and two expression quantitative trait loci (eQTL) SNPs for COL22A1 (rs11784270 A/C and rs6577958 T/C) were analyzed using the TaqMan SNP Genotyping Assay. rs11784270 [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.27-2.62, P = 0.0006] and rs6577958 (OR = 1.45, 95% CI = 1.10-1.94, P = 0.0083) were significantly associated with muscle injury under A and T allele additive genetic models, respectively. These results suggest that the expression level of COL22A1 at the MTJ influences muscle injury risk in athletes.
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Atletas , Colágeno/genética , Músculos/lesiones , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Adolescente , Alelos , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Japón/epidemiología , Masculino , Fenotipo , Saliva , Traumatismos de los Tejidos Blandos/epidemiología , Traumatismos de los Tejidos Blandos/genética , Adulto JovenRESUMEN
Cutaneous wound is a soft tissue injury that is difficult to heal during aging. It has been demonstrated that adipose-derived stem cells (ADSCs) and its secreted exosomes exert crucial functions in cutaneous wound healing. The present study aimed to elucidate the mechanism of exosomes derived from ADSCs (ADSC-Exos) containing MALAT1 in wound healing. ADSCs were isolated from human normal subcutaneous adipose tissues and identified by flow cytometry analysis. Exosomes were extracted from ADSC supernatants and MALAT1 expression was determined using qRT-PCR analysis. HaCaT and HDF cells were exposed to hydrogen peroxide (H2O2) for simulating the skin lesion model. Subsequently, CCK-8, flow cytometry, wound healing and transwell assays were employed to validate the role of ADSC-Exos containing MALAT1 in the skin lesion model. Besides, cells were transfected with sh-MALAT1 to verify the protective role of MALAT1 in wound healing. The binding relationship between MALAT1 and miR-124 were measured by dual-luciferase reporter assay. ADSC-Exos promoted cell proliferation, migration, and inhibited cell apoptosis of HaCaT and HDF cells impaired by H2O2. However, the depletion of MALAT1 in ADSC-Exos lose these protective effects on HaCaT and HDF cells. Moreover, miR-124 was identified to be a target of MALAT1. Furthermore, ADSC-Exos containing MALAT1 could mediate H2O2-induced wound healing by targeting miR-124 and activating Wnt/ß-catenin pathway. ADSC-Exos containing MALAT1 play a positive role in cutaneous wound healing possibly via targeting miR-124 through activating the Wnt/ß-catenin pathway, which may provide novel insights into the therapeutic target for cutaneous wound healing.
Asunto(s)
Exosomas/metabolismo , Fibroblastos/metabolismo , Queratinocitos/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Traumatismos de los Tejidos Blandos/metabolismo , Células Madre/metabolismo , Grasa Subcutánea/citología , Vía de Señalización Wnt , Cicatrización de Heridas , Apoptosis , Movimiento Celular , Proliferación Celular , Exosomas/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Células HaCaT , Humanos , Peróxido de Hidrógeno/toxicidad , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Traumatismos de los Tejidos Blandos/genética , Traumatismos de los Tejidos Blandos/patologíaRESUMEN
OBJECTIVES: To investigate the functional effect of implicated variants within BGN and COL5A1 on gene expression of components of the extracellular matrix (ECM) in a TGF-ß-stimulated risk model for musculoskeletal soft tissue injuries. DESIGN: Experimental research, laboratory study. METHODS: Skin biopsies were obtained from nine healthy participants with either a combined increased or reduced risk profile for COL5A1 rs12722 C>T and BGN rs1126499 C>T - rs1042103 G>A, and primary fibroblast cell lines were established. Total RNA was extracted at baseline (10% FBS), after serum starvation (1% FBS) and TGF-ß1 treatment (1% FBS, 10ng/mL TGF-1ß). Relative mRNA levels of BGN, COL5A1, DCN and VEGFA was quantified using Taqman® array pre-spotted plate assays (Applied Biosystems, Foster city, CA, USA). RESULTS: At baseline, the reduced risk group had 2.5, 1.9 and 2 fold increases (p<0.001) in relative BGN, COL5A1 and VEGFA mRNA levels respectively. In the serum starved experiments, except for a significant 1.5 fold (p=0.017) increase in relative DCN mRNA expression in the reduced risk group, similar observations were noted for the other three genes. After TGF-1ß treatment, the reduced risk group had 1.3 (p=0.011) and 1.4 fold (p=0.001) increases in the relative COL5A1 and VEGFA mRNA levels, respectively. CONCLUSIONS: Altered mRNA levels associated with genetic risk profiles for musculoskeletal soft injury risk at baseline (BGN, COL5A1 and VEGFA), with serum starvation (DCN) and after TGF-ß1 treatment (COL5A1 and VEGFA) provide additional functional evidence to support the association of implicated genetic loci with several musculoskeletal soft tissue injuries. Implication of altered gene expression profiles underpinning these genetic risk associated loci potentially highlight key therapeutic targets for management of these injuries.
Asunto(s)
Biglicano/genética , Colágeno Tipo V/genética , Proteoglicanos/genética , Traumatismos de los Tejidos Blandos/genética , Factor de Crecimiento Transformador beta1/farmacología , Línea Celular , Femenino , Expresión Génica , Genotipo , Voluntarios Sanos , Humanos , Masculino , Factores de Riesgo , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
PURPOSE: Muscle injuries are common in professional football, even though prevention protocols are being implemented. Genetics constitutes a novel field for studying intrinsic injury risks and performance. Since previous studies involving single nucleotide polymorphisms (SNPs) have shown that SNPs influence muscle injury rate, injury severity and recovery time, the aim was to study the association the SNP of ACTN3 has with those parameters in professional football players. METHODS: The medical staff team recorded non-contact musculoskeletal soft-tissue injuries in 43 professional football players in 7 different seasons (2007-2012 and 2015-2016). Injury rate, injury severity and injury recovery times were established. Players were genotyped by extracting DNA from a blood sample and using a polymerase chain reaction. RESULTS: Injury rate was associated with the SNP of ACTN3 (p = 0.003). The 577R allele was more frequent in subjects than in a normal population by showing presence in 93% of the subjects and suggesting that it could influence football performance. No statistically significant differences in injury severity and recovery time were associated with the SNP of ACTN3. CONCLUSIONS: Genetics is gaining in importance when assessing injury risk and performance in professional football. ACTN3 can be regarded as a biomarker of injury susceptibility in this discipline. Identifying those players with the highest injury susceptibility through genetics could lead football teams to individualise workloads and prevention protocols. LEVEL OF EVIDENCE: III.
Asunto(s)
Actinina/genética , Polimorfismo de Nucleótido Simple , Fútbol/lesiones , Traumatismos de los Tejidos Blandos/genética , Adulto , Alelos , Marcadores Genéticos , Genotipo , Humanos , Incidencia , Masculino , España , Adulto JovenRESUMEN
Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue injuries. However, the healing mechanism is unclear. Here we assessed the effects of HBO on contused calf muscles in a rat skeletal muscle injury model. An experimental HBO chamber was developed and rats were treated with 100% oxygen, 2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb volume and muscle wet weight in contused muscles, and promoted muscle isometric strength 7 days after injury. HBO suppressed the elevation of circulating macrophages in the acute phase and then accelerated macrophage invasion into the contused muscle. This environment also increased the number of proliferating and differentiating satellite cells and the amount of regenerated muscle fibers. In the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused muscles. Our results demonstrate that HBO has a dual role in decreasing inflammation and accelerating myogenesis in muscle contusion injuries.
Asunto(s)
Oxigenoterapia Hiperbárica/métodos , Macrófagos/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Oxígeno/farmacología , Células Satélite del Músculo Esquelético/efectos de los fármacos , Traumatismos de los Tejidos Blandos/terapia , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Inflamación , Interleucina-6/genética , Interleucina-6/metabolismo , Contracción Isométrica/efectos de los fármacos , Contracción Isométrica/fisiología , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Desarrollo de Músculos/efectos de los fármacos , Desarrollo de Músculos/genética , Músculo Esquelético/lesiones , Músculo Esquelético/metabolismo , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Regeneración/efectos de los fármacos , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/metabolismo , Transducción de Señal , Traumatismos de los Tejidos Blandos/genética , Traumatismos de los Tejidos Blandos/metabolismo , Traumatismos de los Tejidos Blandos/patologíaRESUMEN
BACKGROUND: Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in elite rugby athletes, we hypothesised that both SNPs would be associated with career success. RESULTS: In 1105 participants (RugbyGene project), comprising 460 elite rugby union (RU), 88 elite rugby league athletes and 565 non-athlete controls, DNA was collected and genotyped for the COL5A1 rs12722 and rs3196378 variants using real-time PCR. For rs12722, the injury-protective CC genotype and C allele were more common in all athletes (21% and 47%, respectively) and RU athletes (22% and 48%) than in controls (16% and 41%, P ≤ 0.01). For rs3196378, the CC genotype and C allele were overrepresented in all athletes (23% and 48%) and RU athletes (24% and 49%) compared with controls (16% and 41%, P ≤ 0.02). The CC genotype in particular was overrepresented in the back and centres (24%) compared with controls, with more than twice the odds (OR = 2.25, P = 0.006) of possessing the injury-protective CC genotype. Furthermore, when considering both SNPs simultaneously, the CC-CC SNP-SNP combination and C-C inferred allele combination were higher in all the athlete groups (≥18% and ≥43%) compared with controls (13% and 40%; P = 0.01). However, no genotype differences were identified for either SNP when RU playing positions were compared directly with each other. CONCLUSION: It appears that the C alleles, CC genotypes and resulting combinations of both rs12722 and rs3196378 are beneficial for rugby athletes to achieve elite status and carriage of these variants may impart an inherited resistance against soft tissue injury, despite exposure to the high-risk environment of elite rugby. These data have implications for the management of inter-individual differences in injury risk amongst elite athletes.
Asunto(s)
Atletas , Colágeno Tipo V/genética , Fútbol Americano , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Traumatismos de los Tejidos Blandos/genética , Adulto , Alelos , Haplotipos , Humanos , MasculinoRESUMEN
We examined the effect of hydroxysafflor yellow A (HSYA) on the inflammatory response to strike-induced acute soft tissue injury in rats. Soft tissue injury was induced in rat leg muscles using a strike hammer, followed by intraperitoneal administration of HSYA at 16, 32, or 64 mg/kg. After 24 h, the rats were anaesthetized, blood and muscle samples were taken. Plasma levels of interleukin (IL)-6, IL-1ß, and tumour necrosis factor (TNF)-αwere measured by enzyme-linked immunosorbent assay. Total RNA and protein were isolated from muscle tissue to determine the mRNA levels of IL-6, IL-1ß, TNF-α, vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1, and the protein level of phosphorylated p38 mitogen-activated protein kinase (MAPK). Nuclear factor (NF)-κB expression was determined by muscle histopathology and immunohistochemistry. HSYA attenuated pathologic changes instrike-induced soft tissue inflammation. Treatment with HSYA also alleviated strike-induced increases in TNF-α, IL-1ß, IL-6, VCAM-1, and ICAM-1mRNA levels and inhibited the increased activation of NF-κB and phosphorylation of p38 MAPK in muscle tissue. These findings suggest that HSYA effectively inhibits strike-induced inflammatory signal transduction in rats.
Asunto(s)
Chalcona/análogos & derivados , Citocinas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/genética , Inflamación/patología , Quinonas/uso terapéutico , Traumatismos de los Tejidos Blandos/genética , Enfermedad Aguda , Animales , Chalcona/química , Chalcona/farmacología , Chalcona/uso terapéutico , Citocinas/sangre , Citocinas/metabolismo , Activación Enzimática/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Músculos/efectos de los fármacos , Músculos/patología , Quinonas/química , Quinonas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Traumatismos de los Tejidos Blandos/patología , Factor de Transcripción ReIA/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Matrix metalloproteinase-3 (MMP3) is a mediator of matrix remodelling and a proposed susceptibility locus in the genetic profile of musculoskeletal soft tissue injuries. Therefore, this study aimed to validate the MMP3 gene as a risk marker for these injuries by conducting a case control genetic association study in two independent samples groups. Three previously investigated MMP3 variants (rs679620, rs591058 and rs650108) in addition to the functional promoter variant (rs3025058) were genotyped in 195 Australian control participants and 79 Australian individuals with chronic Achilles tendinopathy. Similarly, 234 South African individuals with acute anterior cruciate ligament ruptures and 232 matched control participants were also analysed. Based on high linkage with the previously associated MMP3 variant rs679620, rs3025058 was inferred and found to be associated with increased risk for Achilles tendinopathy within the South African group (P = 0.012; OR: 2.88; 95% CI: 1.4 to 6.1). Lastly, the 6A-G-C-G haplotype, constructed from the investigated variants, was significantly associated with reduced risk for Achilles tendinopathy (29% CON vs. 20% TEN, P = 0.037) in the Australian group. In conclusion, a signal surrounding MMP3 is apparent with respect to Achilles tendinopathy. However, whether the investigated variants are contributing to injury susceptibility or whether they are merely linked to the risk conferring variants mapping elsewhere within the MMP gene cluster on chromosome 11, still requires refining.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior/genética , Variación Genética , Genotipo , Metaloproteinasa 3 de la Matriz/genética , Traumatismos de los Tejidos Blandos/genética , Tendinopatía/genética , Tendón Calcáneo , Adulto , Ligamento Cruzado Anterior , Australia , Cromosomas Humanos Par 11 , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , SudáfricaRESUMEN
There is mounting evidence suggesting a genetic contribution to the susceptibility of sustaining a musculoskeletal soft-tissue injury. To date, more than 70 loci have been implicated in several injury profiles. The genes implicated through these loci encode a broad spectrum of matrix proteins including collagens and non-collagens. The large majority of these studies have followed a candidate gene case-control study design. A small proportion of these loci have been repeated in independent studies, of which some have included different musculoskeletal injuries. However, the large majority of these studies are underpowered to detect contributions of small effect sizes (odds ratio <2.0). It is therefore critical that large data sets are collected and that consortia are established to effectively pool resources to understand the biological significance of these genetic loci and risk susceptibility. We are in the era of omics and high-throughput technologies but it is only through collaborations that we will realize the clinical significance of the genomic revolution and its application to musculoskeletal soft-tissue injury susceptibility.
Asunto(s)
Traumatismos en Atletas/genética , Traumatismos de los Tejidos Blandos/genética , Apoptosis , Colágeno/genética , Citocinas/genética , Matriz Extracelular/genética , Humanos , Metaloproteinasas de la Matriz/genética , Polimorfismo Genético , Proteoglicanos/genética , Factores de RiesgoRESUMEN
Genetic factors have been shown to associate with various exercise-related phenotypes, including exercise performance, adaptation to training and sports injuries. The genes implicated in the pathogenesis of musculoskeletal soft-tissue injuries all code for either structural components or regulatory components of the extracellular matrix. It has been hypothesized that these genetic associations with injuries are due to genetically regulated changes in mechanical properties of musculoskeletal soft tissue. Thus, the objective of this review is to highlight the research which has advanced our understanding of how genetic variation within these structural genes affects the properties of our connective tissue. The genetics of various exercise-related phenotypes, such as range of motion, endurance performance and exercise-associated muscle cramps, are reviewed. Lastly, a model is presented where genetic variations within a collagen-encoding gene result in a continuum of phenotype ranging from a normal tissue to a seriously deleterious or lethal disorder.
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Ejercicio Físico , Matriz Extracelular/genética , Variación Genética , Traumatismos de los Tejidos Blandos/genética , Traumatismos en Atletas , Colágeno/genética , Humanos , Músculo Esquelético/lesiones , Músculo Esquelético/fisiología , Fenotipo , Resistencia Física/genética , Rango del Movimiento ArticularRESUMEN
Evidence from familial and genetic association studies have reported that DNA sequence variants play an important role, together with non-genetic factors, in the aetiology of both exercise-associated and occupational-associated acute and chronic musculoskeletal soft tissue injuries. The associated variants, which have been identified to date, may contribute to the interindividual variation in the structure and, by implication, mechanical properties of the collagen fibril and surrounding matrix within musculoskeletal soft tissues, as well as their response to mechanical loading and other stimuli. Future work should focus on the establishment of multidisciplinary international consortia for the identification of biologically relevant variants involved in modulating injury risk. These consortia will improve the limitations of the published hypothesis-driven genetic association studies, since they will allow resources to be pooled in recruiting large well-characterised cohorts required for whole-genome screening. Finally, clinicians and coaches need to be aware that many direct-to-consumer companies are currently marketing genetic tests directly to athletes without it being requested by an appropriately qualified healthcare professional, and without interpretation alongside other clinical indicators or lifestyle factors. These specific genetic tests are premature and are not necessarily required to evaluate susceptibility to musculoskeletal soft tissue injury. Current practice should rather consider susceptibility through known risk factors such as a positive family history of a specific injury, a history of other tendon and/or ligament injuries and participation in activities associated with the specific musculoskeletal injuries. Potential susceptible athletes may then be individually managed to reduce their risk profile.
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Sistema Musculoesquelético/lesiones , Traumatismos de los Tejidos Blandos/genética , Colágeno/genética , Variaciones en el Número de Copia de ADN/genética , Predicción , Variación Genética/genética , Humanos , Polimorfismo Genético/genética , Factores de RiesgoRESUMEN
Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing. Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Prótesis Articulares de Metal sobre Metal/efectos adversos , Mutación/efectos de los fármacos , Traumatismos de los Tejidos Blandos/genética , Anciano , Cromo/efectos adversos , Cromo/sangre , Cobalto/efectos adversos , Cobalto/sangre , Hibridación Genómica Comparativa , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Janus Quinasa 2/genética , Imagen por Resonancia Magnética , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Receptor Notch1/genética , Traumatismos de los Tejidos Blandos/inducido químicamenteRESUMEN
OBJECTIVE: To observe the effect of acupuncture stimulation of Ashi-point on hepatocyte growth factor (HGF) protein expression in gastrocnemius muscle (GM) in rats with traumatic injury of GM, so as to reveal its mechanism underlying improvement of traumatic injury of skeletal muscle. METHODS: A total of 80 SD rats were randomly divided into normal control (n = 8), model, acupuncture control, and acupuncture treatment groups, and the latter 3 groups were further allocated to 0 h, 24 h and 48 h subgroups (n = 8 in each subgroup). The acute soft tissue contusion model was established by using 500 g-counterweight free falling hitting at the GM of the right leg (height 30 cm). The Ashi-point was punctured with a piece of filiform needle by penetrating the site beside the injured GM, and stimulated for about 5 seconds. For acupuncture control group, acupuncture was performed in the same Ashi-point in normal rats. Pathological changes of the focal GM were observed by H. E. staining and HGF protein expression of GM was detected by Western blot. RESULTS: H.E. staining showed that different degrees of injury of GM tissue including broken muscle fibers with cellular swelling, inflammatory cell infiltration, muscle fibrinolysis, atrophy, degeneration and necrosis, etc., were found at each time-point after modeling, while in the acupuncture treatment group, the severity of muscle injury was relatively milder particularly at the time-points of 24 h and 48 h. Compared with the normal control group, HGF protein expression levels of GM at the 3 time-points in the model group, and at 48 h in the acupuncture control group were markedly increased (P<0.05, P<0.01); while in comparison with the model group, HGF protein expression levels were remarkably down-regulated at 24 h and 48 h after acupuncture treatment (P<0.01, P<0.05). CONCLUSION: Acupuncture stimulation of Ashi-point can significantly down-regulate HGF protein expression in the GM in soft tissue contusion rats, which may contribute to its effects in relieving contusion injury of skeletal muscle.
Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Contusiones/terapia , Factor de Crecimiento de Hepatocito/metabolismo , Traumatismos de los Tejidos Blandos/terapia , Animales , Contusiones/genética , Contusiones/metabolismo , Femenino , Factor de Crecimiento de Hepatocito/genética , Humanos , Masculino , Músculo Esquelético/metabolismo , Ratas , Ratas Sprague-Dawley , Traumatismos de los Tejidos Blandos/genética , Traumatismos de los Tejidos Blandos/metabolismoRESUMEN
Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.
Asunto(s)
Proteína Morfogenética Ósea 5/genética , Fracturas Óseas/genética , Expresión Génica/genética , Secuencias Reguladoras de Ácidos Nucleicos , Traumatismos de los Tejidos Blandos/genética , Animales , Humanos , Masculino , Ratones TransgénicosRESUMEN
BACKGROUND AND OBJECTIVE: The prevention, diagnosis, and management of non-contact musculoskeletal soft tissue injuries (NCMSTIs) related to participation in sports are key components of sport and exercise medicine. Epidemiological data have demonstrated the existence of interindividual differences in the severity of NCMSTIs, indicating that these injuries occur as a consequence of both extrinsic and intrinsic factors, including genetic variations. SUBJECTS AND METHODS: We have collected data on NCMSTIs suffered by 73 elite players of White, black African and Hispanic ethnicity of European football over the course of three consecutive seasons. We have also examined eight single nucleotide polymorphisms (SNPs) in genes related to tissue recovery and tissue repair in blood drawn from the players and correlated our findings with type and severity of injuries in each ethnic group. RESULTS: The frequency of the SNPs varied among the three ethnic sub-groups (p<0.0001). Among Whites, a significant relationship was observed between ligament injuries and ELN (p=0.001) and between tendinous injuries and ELN (p=0.05) and IGF2 (p=0.05). Among Hispanics, there was a significant relation between muscle injuries and ELN (p=0.032) and IGF2 (p=0.016). CONCLUSIONS: Interracial genotypic differences may be important in the study of NCMSTIs. A genetic profile based on SNPs may be useful tool to describe each individual's injuribility risk and provide specific treatment and preventive care for football players.
Asunto(s)
Etnicidad/genética , Polimorfismo de Nucleótido Simple , Fútbol/lesiones , Traumatismos de los Tejidos Blandos/genética , Adulto , Alelos , Población Negra/genética , Quimiocina CCL2/genética , Análisis Mutacional de ADN , Elastina/genética , Europa (Continente) , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Factor II del Crecimiento Similar a la Insulina/genética , Ligamentos/lesiones , Masculino , Traumatismos de los Tejidos Blandos/etnología , España/epidemiología , Índices de Gravedad del Trauma , Población Blanca/genéticaRESUMEN
BACKGROUND: The biological mechanisms involved in non-contact musculoskeletal soft tissue injuries (NCMSTI) are poorly understood. Genetic risk factors may be associated with susceptibility to injuries, and may exert marked influence on recovery times. METHODS: Data on type and degree of injury and recovery time were collected in 73 male professional soccer players (43 White, 11 Black Africans and 19 Hispanics) who suffered total of 242 injuries (203 muscle, 24 ligament, and 15 tendon injuries). One single nucleotide polymorphism (SNPs) in the following genes were analyzed: Elastin (ELN); Titin (TTN); SRY-related HMG-box (SOX15); Insulin-like growth factor 2 (IGF2); Chemokine, CC motif, ligand 2 (CCL2); Collagen type 1 alpha 1(COL1A1); Collagen type 5 alpha 1 (COL5A1), and Tenascin C (TNC). RESULTS: There was evidence of a statistically significant association between the degree of injury and the IGF2 genotype (P = 0.034). In addition, there was evidence of a statistically significant association between the degree of muscle injury and CCL2 (P = 0.026) Finally, there was evidence of a statistically significant association between ELN and degree of injury (p = 0.009) and recovery time (P = 0.043). There was no evidence of a statistically significant association between any of the genes studied and degree of injury or recovery time for tendon injuries. CONCLUSION: SNPs in the IGF2, CCL2, and ELN genes may be associated to the degree and recovery time of NCMSTI.
Asunto(s)
Traumatismos en Atletas/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Fútbol , Traumatismos de los Tejidos Blandos/genética , Adulto , Traumatismos en Atletas/patología , Traumatismos en Atletas/fisiopatología , Quimiocina CCL2/genética , Elastina/genética , Genotipo , Humanos , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Recuperación de la Función , Traumatismos de los Tejidos Blandos/patología , Traumatismos de los Tejidos Blandos/fisiopatología , Factores de Tiempo , Índices de Gravedad del Trauma , Adulto JovenRESUMEN
Musculoskeletal soft tissue injuries such as Achilles tendinopathy and anterior cruciate ligament ruptures are common among elite athletes, recreational athletes and physically active individuals. The consequences of injury may be devastating and prevent the recreational or competitive athlete from reaching their potential or lead to a premature end to their careers. Although these injuries have been well described at a clinical level, the biological mechanisms causing these injuries are poorly understood. A further understanding of the biological mechanisms underlying the injury will assist the treatment and management of these injuries. In addition, understanding the biology is an important prerequisite in developing models that can be used to effectively identify risk, as well as, implement personalized prevention, treatment and rehabilitation programmes. Both intrinsic, including genetic variants, and extrinsic risk factors have nevertheless been implicated in the aetiology of these injuries. To date, several patents have been filed which involve the use of specific polymorphisms and regions within specific genes to be used in a genetic test for either tendon or ligament injury risk. The objective of this manuscript will be to review the evidence for the genetic predisposition to soft tissue injury, as well as the application of this data in the prevention, treatment and management of musculoskeletal soft tissue injuries.