Bone Fragility in Hereditary Connective Tissue Disorders: A Systematic Review and Meta-Analysis

Charoenngam, Nipith; Rittiphairoj, Thanitsara; Ponvilawan, Ben; Jaroenlapnopparat, Aunchalee; Waitayangkoon, Palapun; Suppakitjanusant, Pichatorn; Prasitsumrit, Vitchapong; Pongchaiyakul, Chatlert; Holick, Michael F.

doi:10.1016/j.eprac.2023.02.003

Cited by 5 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heritable fragile bone disorders (FBD), which are generally associated with increased fracture risk, range from common multifactorial conditions to rare monogenic diseases (Charoenngam et al ., 2023). They present within a wide phenotypic spectrum where monogenic disorders are generally more severe and often include skeletal deformities and extra-skeletal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

Debaenst,

Jarayseh,

de Saffel

et al. 2024

Preprint

View full text Add to dashboard Cite

Heritable Fragile Bone Disorders (FBDs) encompass a spectrum of conditions, from widespread multifactorial to rare monogenic diseases, all characterized by an elevated risk of fractures. The process of validating causative genes and elucidating their pathogenic mechanisms remains a daunting and resource-intensive task. In this study, we evaluated the feasibility of a semi-high throughput zebrafish screening platform for rapid validation andin vivofunctional testing and validation of candidate disease-causing genes for a wide range of heritable FBDs. Six genes associated with severe recessive forms of Osteogenesis Imperfecta (OI) and four genes associated with BMD, a key osteoporosis indicator, identified through genome-wide association studies (GWAS) were selected. The crispant screening approach, based on CRISPR/Cas9 technology, was used to phenotype directly in F0 mosaic founder zebrafish. Next-Generation Sequencing (NGS) analysis revealed a mean indel efficiency of 88% across ten different crispants, indicating a high proportion of knock-out alleles and thus resembling stable knock-out models. We applied multiple techniques to evaluate skeletal characteristics at 7, 14 and 90 days post-fertilization (dpf), including microscopy for osteoblast reporter visualization and mineralization by Alizarin Red S staining, and microCT for quantitative skeletal analysis. While larval crispants exhibited variable differences in osteoblast-positive and mineralized surface areas, adult-stage crispants displayed more pronounced and consistent skeletal phenotypes. Notably, all crispants developed malformed neural and haemal arches, with a majority presenting vertebral fractures and fusions, and some showing significant alterations in vertebral bone volume and density. In addition,aldh7a1andmbtps2crispants experienced increased mortality due to severe skeletal deformities. RT-qPCR analysis of osteoblast differentiation and bone formation markers at larval stages indicated differential expression of osteogenic markersbglapandcol1a1ain a substantial portion of the crispants, hinting at their utility as biomarkers for FBD crispant screening. In summary, our findings demonstrate that crispant screening in zebrafish offers a viable and efficient strategy for the functional assessment of FBD genes. We advocate for a comprehensive approach that integrates various techniques and evaluates distinct skeletal and molecular profiles across different developmental and adult stages. This methodology has the potential to provide new insights into the role of these genes in skeletal biology.

show abstract

Section: Introductionmentioning

confidence: 99%

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

Debaenst,

Jarayseh,

de Saffel

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Radiologic and histopathologic effects of favipiravir and hydroxychloroquine on fracture healing in rats

Tekçe,

Arıcan,

Karaduman

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Fracture healing is a process in which many factors interact. In addition to many treatments, physical and biological therapy methods that affect different steps of this process, there are many biological and chemical agents that cause fracture union delay. Although the number of studies on fracture healing is increasing day by day, the mechanism of fracture healing, which is not fully understood, still attracts the attention of all researchers. In this study, we aimed to investigate the effects of favipiravir and hydroxychloroquine used in the treatment of COVID-19. In this study, 48 male Wistar rats weighing 300 ± 50 g were used. Each group was divided into eight subgroups of six rats each to be sacrificed at the 2nd and 4th weeks and evaluated radiologically and histologically. Favipiravir (group 1), hydroxychloroquine (group 2), favipiravir + hydroxychloroquine (group 3), and random control (group 4) were used. A statistically significant difference was observed between the 15th day histological scoring averages of the groups (p < 0.05). Although there was no statistically significant difference between the 15th day radiological score distributions of the groups (p > 0.05), we obtained different results in terms of complete bone union distributions and radiological images of the fracture line. Although favipiravir has a negative effect on fracture union in the early period, favipiravir may have a positive effect on fracture union in the late period. We did not find any effect of hydroxychloroquine on fracture union.

show abstract

Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know

Busse,

Lee,

Nagamani

2024

Curr Osteoporos Rep

View full text Add to dashboard Cite

Bone Fragility in Hereditary Connective Tissue Disorders: A Systematic Review and Meta-Analysis

Cited by 5 publications

References 52 publications

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

Radiologic and histopathologic effects of favipiravir and hydroxychloroquine on fracture healing in rats

Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know

Contact Info

Product

Resources

About