Biochemical factors and clubfoot

NewsBot · Aug 13, 2011

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A preliminary study pointing out the role of serum prolidase activity and oxidative-antioxidative status parameters during the treatment process of patients with idiopathic clubfoot.
Altay MA, Erturk C, Aksoy N, Taskın A, Isıkan UE.
Scand J Clin Lab Invest. 2011 Aug 11.

Background. We aimed to investigate serum prolidase activity and to find out its association with oxidative-antioxidative status in patients with idiopathic clubfoot and during the course of the disease.

Material and methods. Oxidative status parameters, including total free sulfhydryl groups (-SH), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI), as well as serum prolidase activity were assessed at the beginning of the treatment in patients with idiopathic clubfoot (n = 38), at the end of 3 months during the treatment of the disease and in healthy controls (n = 40). All patients were managed with the Ponseti method and severity of the foot deformity was evaluated according to the Pirani Severity Score.

Results. Serum prolidase activity, TOS and OSI values of the patients at the beginning of the treatment were found to be significantly higher but -SH and TAC values were found to be significantly lower as compared to controls. In the treatment process, a significant decrease in serum prolidase activity, TOS and OSI values and Pirani Severity Score of the patients was observed, however a significant increase in -SH and TAC values of the patients was observed at the end of 3 months during the treatment of the disease as compared to the beginning of the treatment.

Conclusion. Elevated levels of serum prolidase activity, TOS and OSI, and decreased levels of -SH and TAC may be associated with idiopathic clubfoot, and that these parameters may be useful adjunctive tools for follow-up in patients with idiopathic clubfoot.
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NewsBot · Mar 2, 2017

Possible pathogenetic mechanisms and new therapeutic approaches of Pes Equinovarus.
Ošťádal M et al
Physiol Res. 2017 Feb 28.

Idiopathic pes equinovarus (clubfoot) is a congenital deformity of the foot and lower leg defined as a fixation of the foot in plantar flexion, adduction, supination and varus. The deformity does not affect only the foot position, which is usually investigated by radiography, CT, micro-CT, MRI or ultrasound but logically influence the whole gait biomechanics. It is supposed, that clubfoot belongs to a group of fibroproliferative disorders whose origin and multi-hierarchical effect remain unknown. It has been suggested that fibroblasts and growth factors may be involved. To gain a more global view, direct analysis of the protein composition of extracellular matrix, a proteomic approach was used. At present two principle methods are mostly used for the treatment of clubfoot: physiotherapy and the Ponseti method. The determination of the general biological and biomechanical parameters for various regions of the clubfoot can potentially help in the understanding of the mechanisms participating on this serious anomaly and thus contribute to the development of the more efficient therapeutic approach. This review summarizes the present knowledge on the possible pathogenetic mechanisms participating in the development of the clubfoot and their possible relation to the new therapeutic approaches.
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NewsBot · Jan 26, 2020

Integrated bioinformatics analysis of potential pathway biomarkers using abnormal proteins in clubfoot
Guiquan Cai et al
January 20, 2020

Background
As one of the most common major congenital distal skeletal abnormalities, congenital talipes equinovarus (clubfoot) affects approximately one in one thousandth newborns. Although several etiologies of clubfoot have been proposed and several genes have been identified as susceptible genes, previous studies did not further explore signaling pathways and potential upstream and downstream regulatory networks. Therefore, the aim of the present investigation is to explore abnormal pathways and their interactions in clubfoot using integrated bioinformatics analyses.

Methods
KEGG, gene ontology (GO), Reactome (REAC), WikiPathways (WP) or human phenotype ontology (HP) enrichment analysis were performed using WebGestalt, grofiler and NetworkAnalyst.

Results
A large number of signaling pathways were enriched e.g. signal transduction, disease, metabolism, gene expression (transcription), immune system, developmental biology, cell cycle, and ECM. Protein-protein interactions (PPIs) and gene regulatory networks (GRNs) analysis results indicated that extensive and complex interactions occur in these proteins, enrichment pathways, and TF-miRNA coregulatory networks. Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins.

Conclusion
The results of the present study supported previously proposed hypotheses, such as ECM, genetic, muscle, neurological, skeletal, and vascular abnormalities. More importantly, the enrichment results also indicated cellular or immune responses to external stimuli, and abnormal molecular transport or metabolism may be new potential etiological mechanisms of clubfoot.
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NewsBot · Nov 30, 2021

Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies
Jarmila Knitlova et al
Int J Mol Sci. 2021 Nov 2;22(21):11903

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.
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NewsBot · May 4, 2022

The possible role of hypoxia in the affected tissue of relapsed clubfoot
Tomas Novotny, Adam Eckhardt, Martina Doubkova, Jarmila Knitlova, David Vondrasek, Eliska Vanaskova, Martin Ostadal, Jiri Uhlik, Lucie Bacakova & Jana Musilkova
Scientific Reports volume 12, Article number: 4462 (2022)

Our aim was to study the expression of hypoxia-related proteins as a possible regulatory pathway in the contracted side tissue of relapsed clubfoot. We compared the expression of hypoxia-related proteins in the tissue of the contracted (medial) side of relapsed clubfoot, and in the tissue of the non-contracted (lateral) side of relapsed clubfoot. Tissue samples from ten patients were analyzed by immunohistochemistry and image analysis, Real-time PCR and Mass Spectrometry to evaluate the differences in protein composition and gene expression. We found a significant increase in the levels of smooth muscle actin, transforming growth factor-beta, hypoxia-inducible factor 1 alpha, lysyl oxidase, lysyl oxidase-like 2, tenascin C, matrix metalloproteinase-2, matrix metalloproteinase-9, fibronectin, collagen types III and VI, hemoglobin subunit alpha and hemoglobin subunit beta, and an overexpression of ACTA2, FN1, TGFB1, HIF1A and MMP2 genes in the contracted medial side tissue of clubfoot. In the affected tissue, we have identified an increase in the level of hypoxia-related proteins, together with an overexpression of corresponding genes. Our results suggest that the hypoxia-associated pathway is potentially a factor contributing to the etiology of clubfoot relapses, as it stimulates both angioproliferation and fibroproliferation, which are considered to be key factors in the progression and development of relapses.
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Biochemical factors and clubfoot

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Biochemical factors and clubfoot

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Effect of foot orthotics on biochemical markers of skeletal muscles damage

Biochemical changes in achilles tendinosis

Predictive factors for foot pain

The foot as a lever :Factors influencing stiffness and efficiency

Chronic diseases and allergies as risk factors for MTSS

Impact Factors of Foot and Ankle Journals

Foot Orthotics and Intrinsic Factors on Strain Measurements in the Fifth Metatarsal

Share This Page

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