Collagen VI in the Musculoskeletal System Di Martino, Alberto; Cescon, Matilde; D'Agostino, Claudio ...
International journal of molecular sciences,
03/2023, Volume:
24, Issue:
6
Journal Article
Peer reviewed
Open access
Collagen VI exerts several functions in the tissues in which it is expressed, including mechanical roles, cytoprotective functions with the inhibition of apoptosis and oxidative damage, and the ...promotion of tumor growth and progression by the regulation of cell differentiation and autophagic mechanisms. Mutations in the genes encoding collagen VI main chains,
and
, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise. No effective therapeutic strategy is available so far for these diseases; moreover, the effects of collagen VI mutations on other tissues is poorly investigated. The aim of this review is to outline the role of collagen VI in the musculoskeletal system and to give an update about the tissue-specific functions revealed by studies on animal models and from patients' derived samples in order to fill the knowledge gap between scientists and the clinicians who daily manage patients affected by collagen VI-related myopathies.
Introduction
Recurrent dislocations are still the most frequent reason for revision in total hip arthroplasty (THA). The impact of bearing surfaces on dislocations is still controversial. We ...hypothesized that: (1) bearing surfaces influence the revisions due to dislocations; (2) ceramic-on-ceramic reduced the revisions for dislocations in adjusted models; (3) Delta-on-Delta bearings reduced the revisions for dislocations in comparison to surfaces with cross-linked polyethylene.
Materials and methods
The regional arthroplasty registry was enquired about bearing surfaces and revisions for dislocations and instability. Unadjusted and adjusted rates were provided, including sex, age (<65 years or ≥65 years), head diameter (≤28 mm or >28 mm; <36 mm or ≥36 mm) as variables. 44,065 THAs were included.
Results
The rate of revisions for dislocations was significantly lower in ceramic-on-ceramic and metal-on-metal bearings (unadjusted rates). After adjusting for age, sex, and head size (36 and 28 mm), hard-on-hard bearings were protective (
p
< 0.05): ceramic-on-ceramic had a lower risk of revisions due to dislocation than ceramic-on-polyethylene (HR 1.6, 95% CI 1.2–2.2
p
= 0.0009). The rate of revisions for dislocation was similar in bearings with cross-linked polyethylene and Delta-on-Delta articulations, in unadjusted and adjusted models.
Conclusion
Bearings with conventional polyethylene were more predisposed to dislocations. Currently adopted bearings exerted no significant influence on revisions due to dislocations. These findings could be primarily related to wear, but due to the time distribution, soft tissue envelopes and surface tension may also play a role. Pre-clinical biomechanical evaluations and prospective matched cohort studies are required to draw definitive conclusions.
Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is ...a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.
Pathogenetic mechanism recognition and proof-of-concept clinical trials were performed in our patients affected by collagen VI-related myopathies. This study, which included 69 patients, aimed to ...identify innovative clinical data to better design future trials. Among the patients, 33 had Bethlem myopathy (BM), 24 had Ullrich congenital muscular dystrophy (UCMD), 7 had an intermediate phenotype (INTM), and five had myosclerosis myopathy (MM). We obtained data on muscle strength, the degree of contracture, immunofluorescence, and genetics. In our BM group, only one third had a knee extension strength greater than 50% of the predicted value, while only one in ten showed similar retention of elbow flexion. These findings should be considered when recruiting BM patients for future trials. All the MM patients had axial and limb contractures that limited both the flexion and extension ranges of motion, and a limitation in mouth opening. The immunofluorescence analysis of collagen VI in 55 biopsies from 37 patients confirmed the correlation between collagen VI defects and the severity of the clinical phenotype. However, biopsies from the same patient or from patients with the same mutation taken at different times showed a progressive increase in protein expression with age. The new finding of the time-dependent modulation of collagen VI expression should be considered in genetic correction trials.
Background
Powder technology was developed to bring together the mechanical features and high porosity of titanium. However, the high porosity may theoretically compromise mechanical resistance. ...Literature is deficient about the use and safety profile of cementless femoral implants built using additive manufacturing (in particular electron beam melting technology, EBM). The purpose of this study was to evaluate the survival rates and the reason for revisions (especially implant breakage) of the first two EBM-built stems at a mid-term follow-up, using a joint arthroplasty registry.
Methods
The registry of Prosthetic Orthopedic Implant (RIPO) was investigated about cementless stems implanted from 2010 to 2017. Stems built with EBM technology (Parva and Pulchra stems; Adler Ortho, Milan, Italy) were compared to all the other cementless stems implanted during the same period, acting as control group. The survival rates and reasons for revision were assessed.
Results
No stem breakage occurred. At 5-year follow-up, the survival rates of the two cohorts were not statistically different (96.8% EBM stems, 98.0% standard cementless stems;
p
> 0.05). In the EBM stems, aseptic loosening occurred in 1.7% of the cases at the latest follow-up.
Conclusions
This large cohort showed that mechanical resistance is not a concern in EBM stems at mid-term follow-up. However, larger populations and longer follow-ups are needed to further validate these results.
Adolescent idiopathic scoliosis (AIS) is a three-dimensional structural deformity of the spine that affects 2-3% of adolescents under the age of 16. AIS etiopathogenesis is not completely understood; ...however, the disease phenotype is correlated to multiple genetic loci and results from genetic-environmental interactions. One of the primary, still unresolved issues is the implementation of reliable diagnostic and prognostic markers. For clinical management improvement, predictors of curve progression are particularly needed. Recently, an epigenetic contribution to AIS development and progression was proposed; nevertheless, validation of data obtained in peripheral tissues and identification of the specific mechanisms and genes under epigenetic control remain limited. In this study, we propose a methodological approach for the identification of epigenetic markers of AIS progression through an original workflow based on the preliminary characterization of local expression of candidate genes in tissues directly involved in the pathology. The feasibility of the proposed methodological protocol has been originally tested here in terms of identification of the putative epigenetic markers of AIS progression, collection of the different tissues, retrieval of an appropriate amount and quality of RNA and DNA, and identification of suitable reference genes.
Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain ...and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain is still very challenging. In this regard, there is a growing body of evidence for the role of several bioactive dietary molecules (BDMs) in targeting inflammation and pain, with promising clinical results. BDMs may be valuable non-pharmaceutical solutions to treat and prevent the evolution of early OA to more severe phenotypes, overcoming the side effects of anti-inflammatory drugs. Among BDMs, polyphenols (PPs) are widely studied due to their abundance in several plants, together with their benefits in halting inflammation and pain. Despite their biological relevance, there are still many questionable aspects (biosafety, bioavailability, etc.) that hinder their clinical application. This review highlights the mechanisms of action and biological targets modulated by PPs, summarizes the data on their anti-inflammatory and anti-nociceptive effects in different preclinical in vitro and in vivo models of OA and underlines the gaps in the knowledge. Furthermore, this work reports the preliminary promising results of clinical studies on OA patients treated with PPs and discusses new perspectives to accelerate the translation of PPs treatment into the clinics.
Low back pain is an extremely common condition with severe consequences. Among its potential specific causes, degenerative disc disease (DDD) is one of the most frequently observed. Mechanobiology is ...an emerging science studying the interplay between mechanical stimuli and the biological behavior of cells and tissues. The aim of the presented study is to review, with a systematic approach, the existing literature regarding the mechanobiology of the human intervertebral disc (IVD), define the main pathways involved in DDD and identify novel potential therapeutic targets. The review was carried out in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included if they described biological responses of human IVD cells under mechanical stimulation or alterations of mechanical properties of the IVD determined by different gene expression. Fifteen studies were included and showed promising results confirming the mechanobiology of the human IVD as a key element in DDD. The technical advances of the last decade have allowed us to increase our understanding of this topic, enabling us to identify possible therapeutic targets to treat and to prevent DDD. Further research and technological innovations will shed light on the interactions between the mechanics and biology of the human IVD.
Recently, various studies have reported the importance of distinguishing between balanced and unbalanced SL, sustaining the importance of SL reduction in unbalanced cases. In this study we present ...our experience in the treatment of isthmic spondylolisthesis in young patients, observing the correlation between SL reduction and sagittal correlation between spine and pelvis.
This is a retrospective study of a series of patients treated surgically for isthmic spondylolisthesis. Inclusion criteria were L5-S1 isthmic spondylolisthesis of III° or IV°, pediatric age, clinical and radiographic follow up of at least 1 year. Radiographic evaluation included the following elements: grade and percentage of listhesis (%L), lumbar lordosis (LL), lumbar-sacral angle (LSA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT) distinguishing between "balanced" and "unbalanced" patients. Radiographic values were confronted by using Student's t- test, obtaining a statistically significant difference for values inferior to 0,05.
Based on inclusion criteria, 28 patients were selected for our retrospective analysis, 19 female and 9 male. Mean age at surgery was 15,6 years. Mean follow up was 3 years and 3 months (min. 1 year - max 6 years and 7 months). Spondylolisthesis reduction was statistically significant both in balanced and in unbalanced patients, but pelvic incidence values did not improve significantly. We observed fewer mechanical complications in patients treated with interbody support.
In our study, differences between pre-op and post-op spinopelvic alignment values were not statistically significant, even though spondylolisthesis reduction was statistically significant in all cases. Our study could be considered an initial attempt to correlate spinopelvic changes to spondylolisthesis reduction in a progressive manner, and possibly in the future, generate threshold values of reduction for ideal spinopelvic alignment in every different patient.
Dynamic balance plays a key role in high-impact sports, such as CrossFit, where athletes are required to maintain balance in various weightlifting exercises. The loss of balance in these ...sport-specific movements may not only affect athlete performance, but also increase the risk of injuries.
The aim of the study is to achieve greater insight into the balance and athlete position during the CrossFit training by means of inertial sensors, with a particular focus on the role of different custom foot orthoses (CFOs) in order to detect correlations with the role of the cavus foot.
A total of 42 CrossFit
athletes, aged 25 to 42 years, were enrolled in this study. One-way ANOVA tests with post-hoc analysis of variance were used to compare foot posture groups and effects of different types of customized foot orthoses.
When comparing the effects of CFOs with the respective balance basal level during the pistol squat exercise, we observed a significant (
= 0.0001) decrease in the sway area, antero-posterior displacement (APD) and medio-lateral displacement (MLD) compared to the basal using both types of CFOs.
No significant positive effects of CFOs were observed in some static tests. On the contrary, positive effects of CFOs and, in particular, postural insoles, are relevant to dynamic balance.
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