scholarly journals X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1851
Author(s):  
Petar Brlek ◽  
Darko Antičević ◽  
Vilim Molnar ◽  
Vid Matišić ◽  
Kristina Robinson ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Bone Fractures ◽  
Bone Mineralization ◽  
Severe Disease ◽  
Compression Fracture ◽  
Lumbar Vertebra ◽  
Bone Diseases ◽  
Complex Spectrum ◽  
Minor Trauma ◽  
Sequencing Analysis

Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the pathogenesis of OI caused by mutations in many other genes associated with normal bone mineralization. In this paper, a case of a rare X-linked variant of OI with a change in the gene encoding plastin 3—a protein important for the regulation of the actin cytoskeleton, is presented. A 16-year-old patient developed ten bone fractures caused by minor trauma or injury, including a compression fracture of the second lumbar vertebra during his lifetime. Next-generation sequencing analysis did not show pathologically relevant deviations in the COL1A1 and COL1A2 genes. Targeted gene analyses (Skeletal disorder panel) of the patient, his father, mother and sister were then performed, detecting variants of uncertain significance (VUS) for genes PLS3, FN1 and COL11A2. A variant in the PLS3 gene were identified in the patient, his mother and sister. Since the PLS3 gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the PLS3 gene (c.685G>A (p.Gly229Arg)) has not yet been described in the literature, nor is its pathogenicity known, clinical findings combined with genetic testing showed that this variant may explain the cause of X-linked OI in our patient. This rare case of the PLS3 variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease.

scholarly journals A New Radiographic Method for Estimating Tibial Malrotation

2020 ◽  
Vol 7 (3) ◽  
pp. 121-128
Author(s):  
Hamidreza Yazdi ◽  
◽  
Mohammad Taher Ghaderi ◽  
Alireza Yousof Gomrokchi ◽  
Parham Pezeshk ◽  
...  
Keyword(s):  
Lower Limb ◽  
Evaluation Method ◽  
Bone Fractures ◽  
Distal Tibia ◽  
Bone Diseases ◽  
The Body ◽  
University Hospital ◽  
Radiographic Evaluation ◽  
Minor Trauma ◽  
Lower Limb Injury

Background: Diaphyseal tibial fractures are the most frequent bone fractures in the body and are usually treated with intramedullary nailing method. However, this approach is responsible for 41% of the rotational deviation.  Objectives: This study aimed to provide a radiographic evaluation method to determine tibial malrotation in closed fixation of tibia bone fractures during or after the operation. Methods: This study was conducted in a university hospital from May 2015 to March 2016. All patients referring to the hospital with the complaints of minor trauma around the ankle and knee requiring radiographic evaluation of both joints were enrolled in the study. The inclusion criteria included being 20 and 50 years old; having normal axial, sagittal, and coronal lower limb alignment; lacking previous lower limb injury (such as fractures of the tibia or fibula), ankle or knee sprain; not having previous lower limb surgery, metabolic or congenital bone diseases, or malignancy. In all cases, a standard Anteroposterior (AP) radiograph of the knee was taken, and then, without changing the limb position or image setting, an AP radiograph of the ankle was obtained. The overlap between the distal tibia and fibula was measured in the PACS program environment.   Results: Fifty cases were included in this study. The Mean±SD ages of males and females were 29.08±2.49 years and 31.46±2.04 years, respectively. The range of distal tibia-fibula overlap one centimeter above the tibiotalar joint line was 7.81 to 9.09 mm (confidence interval of 95%), and its percentage to the fibula shaft width at the same level was 49.43% to 54.35%. Conclusion: According to the results, distal tibia-fibula overlap when the knee is in the true AP position, regardless of the side and gender, is 7.81 to 9.09 mm or 49.43% to 54.35%.

Possible Protective Role of Deferoxamine in Ameliorating Osteoporosis in a Rat Model of Liver Cirrhosis via Iron Metabolism Regulation

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Shereen Helmy ◽  
Doaa I Mohamed ◽  
Wesam Elbakly ◽  
Lobna F Abd Elaziz ◽  
Eman Khairy ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Iron Overload ◽  
Rat Model ◽  
Bone Fractures ◽  
Bone Mineralization ◽  
Treated Group ◽  
Disease Etiology ◽  
Iron Storage ◽  
Metabolism Regulation ◽  
Hepatic Diseases

Abstract Background Liver cirrhosis is considered the terminal stage of many hepatic diseases of different etiologies. Liver cirrhosis was associated with increased incidence rates of some extrahepatic manifestations such as osteoporosis. Regardless of the liver disease etiology, the presence of cirrhosis implies a twofold risk of bone fractures higher than non-cirrhotic patients. The liver is the main storage depot for iron and is the primary organ that is responsible for clearing excess iron in conditions of iron overload. When the iron storage and antioxidant capacity of the liver is overwhelmed, iron overload can lead to marked oxidantmediated liver and bone injury and iron overload was a risk factor for osteoporosis via affecting osteoblast survival. Aim of the work to examine the possible protective effect of Deferoxamine (DFO) on liver cirrhosis rat model induced osteoporosis. Material and Method rats was divided into 4 groups Animal Groups: Naïve control, DFO-treated group, TAA-treated group received Thioacetamide (TAA) ip (200 mg/kg/rat) twice weekly for 12 weeks, TAA+DFO treated group received TAA intra-peritoneal in addition to DFO intraperitoneal injections (300 mg/kg/3 times/week, for the last 4 weeks of TAA injections. Results and Conclusion Deferoxamine produced significant improvement in bone mineralization alongside its significant effect on liver function test in a rat model of liver cirrhosis induced osteoporosis.

scholarly journals Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019

2021 ◽  
Vol 12 ◽  
Author(s):  
Furong Qi ◽  
Wenbo Zhang ◽  
Jialu Huang ◽  
Lili Fu ◽  
Jinfang Zhao
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
Severe Disease ◽  
Sequencing Analysis ◽  
Sequencing Data ◽  
Metabolic Remodeling ◽  
Single Cell Rna Sequencing ◽  
Antibody Secretion

Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14+ cells expressed higher levels of glycolysis-related genes (PKM, LDHA and PKM) and PPP-related genes (PGD and TKT) in severe patients than in mild patients. These genes may contribute to the hyperinflammation in mono-CD14+ cells of patients with severe COVID-19. The mono-CD16+ cell population in COVID-19 patients showed reduced transcription levels of genes related to lysine degradation (NSD1, KMT2E, and SETD2) and elevated transcription levels of genes involved in OXPHOS (ATP6V1B2, ATP5A1, ATP5E, and ATP5B), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene ATP13A3 in COVID-19 patients, which was positively associated with antibody secretion and survival of PCs. Moreover, enhanced glycolysis or OXPHOS was positively associated with the differentiation of memory B cells into plasmablasts or plasma cells. This study comprehensively investigated the metabolic features of peripheral immune cells and revealed that metabolic changes exacerbated inflammation in monocytes and promoted antibody secretion and cell survival in PCs in COVID-19 patients, especially those with severe disease.

EFFECTS OF Justicia gendarussa ETHANOLIC EXTRACT ON OSTEOBLASTIC ACTIVITY OF MC3T3-E1 CELL

2015 ◽  
Vol 77 (3) ◽  
Author(s):  
Kavita Supparmaniam ◽  
Siti Pauliena Mohd Bohari
Keyword(s):  
Bone Repair ◽  
Bone Fractures ◽  
Bone Mineralization ◽  
Ethanolic Extract ◽  
Repair Process ◽  
New Bone Formation ◽  
Osteoblast Cells ◽  
Osteoblastic Activity ◽  
Alp Activity ◽  
Ic50 Value

Justicia gendarussa (Acanthaceae) or commonly known as Gendarussa has traditionally been used to treat bone fractures. Bone fracture is a clinical condition that need bone repair and new bone formation. To date, the mechanism of Justicia gendarussa acting in enhancing the bone mineralization has not been proven scientifically. The present study aimed to investigate the cytotoxicity and alkaline phosphatase (ALP) activity on osteoblast cells when treated with Justicia gendarussa ethanolic leaves extract. MTT and ALP assays were performed on osteoblast cells after being treated with different concentrations of the extract. For cell viability, the result showed that IC50 value of the osteoblast cells was 89.1μg/ml. While, ALP assay is used as a biochemical marker for early detection of osteoblast mineralization. The highest amount of ALP activity was at the 37.5 μg/ml when compared to the control. From this study, it shows that Justicia gendarussa has potential in enhancing bone mineralization during the bone repair process.  

scholarly journals Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing

2019 ◽  
Vol 20 (5) ◽  
pp. 1079 ◽  
Author(s):  
Sopak Supakul ◽  
Kenta Yao ◽  
Hiroki Ochi ◽  
Tomohito Shimada ◽  
Kyoko Hashimoto ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Fracture ◽  
Bone Fractures ◽  
Callus Formation ◽  
Bone Diseases ◽  
Lineage Tracing ◽  
Osteogenic Potential ◽  
Bone Fracture Healing ◽  
Osteogenic Cells

Pericytes are mesenchymal cells that surround the endothelial cells of small vessels in various organs. These cells express several markers, such as NG2, CD146, and PDGFRβ, and play an important role in the stabilization and maturation of blood vessels. It was also recently revealed that like mesenchymal stem cells (MSCs), pericytes possess multilineage differentiation capacity, especially myogenic, adipogenic, and fibrogenic differentiation capacities. Although some previous studies have reported that pericytes also have osteogenic potential, the osteogenesis of pericytes can still be further elucidated. In the present study, we established novel methods for isolating and culturing primary murine pericytes. An immortalized pericyte line was also established. Multilineage induction of the pericyte line induced osteogenesis, adipogenesis, and chondrogenesis of the cells in vitro. In addition, pericytes that were injected into the fracture site of a bone fracture mouse model contributed to callus formation. Furthermore, in vivo pericyte-lineage-tracing studies demonstrated that endogenous pericytes also differentiate into osteoblasts and osteocytes and contribute to bone fracture healing as a cellular source of osteogenic cells. Pericytes can be a promising therapeutic candidate for treating bone fractures with a delayed union or nonunion as well as bone diseases causing bone defects.

scholarly journals Zebrafish: A Suitable Tool for the Study of Cell Signaling in Bone

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1911
Author(s):  
Maria Teresa Valenti ◽  
Giulia Marchetto ◽  
Monica Mottes ◽  
Luca Dalle Carbonare
Keyword(s):  
Osteogenesis Imperfecta ◽  
Signaling Pathways ◽  
Gaucher Disease ◽  
Model Organism ◽  
Bone Diseases ◽  
Zebrafish Model ◽  
Bone Differentiation ◽  
Transgenic Lines ◽  
Therapeutic Tools ◽  
Genetic Mutants

In recent decades, many studies using the zebrafish model organism have been performed. Zebrafish, providing genetic mutants and reporter transgenic lines, enable a great number of studies aiming at the investigation of signaling pathways involved in the osteoarticular system and at the identification of therapeutic tools for bone diseases. In this review, we will discuss studies which demonstrate that many signaling pathways are highly conserved between mammals and teleost and that genes involved in mammalian bone differentiation have orthologs in zebrafish. We will also discuss as human diseases, such as osteogenesis imperfecta, osteoarthritis, osteoporosis and Gaucher disease can be investigated in the zebrafish model.

scholarly journals Identification of Free-Living Amoebas in Tap Water of Buildings with Storage Tanks in Korea

2020 ◽  
Vol 58 (2) ◽  
pp. 191-194
Author(s):  
Da-In Lee ◽  
Sung Hee Park ◽  
Jong Hwan Baek ◽  
Jee Won Yoon ◽  
Soo Im Jin ◽  
...  
Keyword(s):  
Tap Water ◽  
Severe Disease ◽  
Human Infection ◽  
Contamination Rate ◽  
Sequencing Analysis ◽  
Storage Tanks ◽  
Species Classification ◽  
Free Living ◽  
E Coli ◽  
Service Areas

Free-living amoebas (FLAs) can cause severe disease in humans and animals when they become infected. However, there are no accurate survey reports on the prevalence of FLAs in Korea. In this study, we collected 163 tap water samples from buildings, apartments, and restrooms of highway service areas in 7 Korean provinces with high population density. All these buildings and facilities have water storage tanks in common. The survey was separated into categories of buildings, apartments, and highway service areas. Five hundred milliliters of tap water from each building was collected and filtered with 0.2 µm pore filter paper. The filters were incubated in agar plates with heated <i>E. coli</i> at 25°C. After axenization, genomic DNA was collected from each FLA, and species classification was performed using partial 18S-rDNA PCR-sequencing analysis. We found that 12.9% of tap water from buildings with storage tanks in Korea was contaminated with FLAs. The highway service areas had the highest contamination rate at 33.3%. All of the FLAs, except one, were genetically similar to <i>Vermamoeba vermiformis</i> (<i>Hartmannella vermiformis</i>). The remaining FLA (KFA21) was very similar to <i>Acanthamoeba lugdunensis</i> (KA/E26). Although cases of human infection by <i>V. vermiformis</i> are very rare, we must pay attention to the fact that one-third of tap water supplies in highway service areas have been contaminated.

scholarly journals Osteogenesis imperfecta and cerebrospinal fluid leak: a unique presentation and treatment challenge

2019 ◽  
Vol 59 (4) ◽  
pp. 74-78
Author(s):  
Clara Mota Randal Pompeu ◽  
Anna Caroline Rodrigues de Souza Matos ◽  
Mirian Mota Randal Pompeu ◽  
Luis Fernando Falcão de Castro Meireles ◽  
Daniel Aguiar Dias ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Osteogenesis Imperfecta ◽  
Bone Fractures ◽  
Clinical Status ◽  
Sella Turcica ◽  
Imaging Study ◽  
Cerebrospinal Fluid Leak ◽  
Signs And Symptoms ◽  
Bone Fragility ◽  
Csf Leak

Introduction: Osteogenesis imperfecta (OI) is a heritable disorder of the connective tissue that mainly manifests as bone fragility. Other signs and symptoms may be present, such as sensorineural hearing loss, cardiac malformations, and teeth alterations. Case description: 72-year-old female patient presented with left abundant spontaneous hyaline rhinorrhea, history of several bone fractures since early childhood, and a blue grayish sclera was noted. Cerebrospinal fluid (CSF) leak was diagnosed. Neuroimaging revealed lowering of the sella turcica floor, platybasia, basilar impression, left middle fossa calcified meningioma, syringobulbia, ventricular dilatation, and left ethmoidal fistula. Due to the patient’s age and clinical status, a medical approach was chosen, and treatment with acetazolamide and furosemide in low dosages, which resulted in a decrease of the rhinorrhea. Discussion: Clinical features and imaging study are often sufficient for diagnosis of OI. The neurological and cranial features in OI are varied. CSF leak is not commonly reported and might have been a consequence of bone softening and hydrocephalus. Conclusions: This case represents a treatment challenge, as the surgical results were uncertain, once bone fragility could result in the development of new leaks. Clinical treatment was chosen and resulted in a significant improvement of the symptoms.

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