scholarly journals The WNT1G177C mutation specifically affects skeletal integrity in a mouse model of osteogenesis imperfecta type XV

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nele Vollersen ◽  
Wenbo Zhao ◽  
Tim Rolvien ◽  
Fabiola Lange ◽  
Felix Nikolai Schmidt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Bone Matrix ◽  
Bone Fragility ◽  
Osteogenesis Imperfecta Type ◽  
Matrix Quality ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Term Administration ◽  
And Function

AbstractThe recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV (OI-XV) has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts. Although such an influence was supported by subsequent studies, a mouse model of OI-XV remained to be established. Therefore, we introduced a previously identified disease-causing mutation (G177C) into the murine Wnt1 gene. Homozygous Wnt1G177C/G177C mice were viable and did not display defects in brain development, but the majority of 24-week-old Wnt1G177C/G177C mice had skeletal fractures. This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality. Importantly, the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5, the latter mimicking the effect of sclerostin neutralization. Finally, transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers. Taken together, our data demonstrate that regulating bone matrix quality is a primary function of WNT1. They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.

scholarly journals Clinic Case of Rare Type VI Osteogenesis Imperfecta

2019 ◽  
Vol 16 (1) ◽  
pp. 30-35
Author(s):  
Olga N. Ignatovich ◽  
Leyla S. Namazova-Baranova ◽  
Tea V. Margieva ◽  
Natalia V. Zhurkova ◽  
Kirill V. Savostyanov ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
High Frequency ◽  
Heterogeneous Group ◽  
Osteogenesis Imperfecta Type ◽  
Post Translational Modification ◽  
Rare Type ◽  
Genes Encoding ◽  
Long Time ◽  
Collagen Genes

Osteogenesis imperfect is genetically heterogeneous group of diseases which are characterized by bone brittleness and fractures. It was thought for a long time that this is happening due to mutations in collagen genes. However, within past decade the understanding of osteogenesis imperfecta etiology has changed as a result of genetics development. The majority of all cases is related to mutations in collagen genes whereas rare mostly recessive forms are related to mutations in genes encoding collagen post-translational modification. Mutations in SERPINF1 gene were chosen as molecular cause of osteogenesis imperfecta type VI in 2011. Thus the new pathophysiology of this disease was revealed. Children with osteogenesis imperfecta type VI have high-frequency of fractures despite the management with bisphosphonates because mineralized bone osteoid is considerably reduced.

scholarly journals Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts

2020 ◽  
Vol 24 (11) ◽  
pp. 3923-3937
Author(s):  
Maria B. Asparuhova ◽  
Vivianne Chappuis ◽  
Alexandra Stähli ◽  
Daniel Buser ◽  
Anton Sculean
Keyword(s):  
Growth Factor ◽  
Osteogenic Differentiation ◽  
Bone Matrix ◽  
Osteogenic Potential ◽  
Differentiation Markers ◽  
Self Renewal ◽  
Downstream Signaling ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
The Impact

Abstract Objectives The aim of the study was to investigate the impact of two hyaluronan (HA) formulations on the osteogenic potential of osteoblast precursors. Materials and methods Proliferation rates of HA-treated mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells were determined by 5-bromo-20-deoxyuridine (BrdU) assay. Expression of genes encoding osteogenic differentiation markers, critical growth, and stemness factors as well as activation of downstream signaling pathways in the HA-treated cells were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunoblot techniques. Results The investigated HAs strongly stimulated the growth of the osteoprogenitor lines and enhanced the expression of genes encoding bone matrix proteins. However, expression of late osteogenic differentiation markers was significantly inhibited, accompanied by decreased bone morphogenetic protein (BMP) signaling. The expression of genes encoding transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-1 (FGF-1) as well as the phosphorylation of the downstream signaling molecules Smad2 and Erk1/2 were enhanced upon HA treatment. We observed significant upregulation of the transcription factor Sox2 and its direct transcription targets and critical stemness genes, Yap1 and Bmi1, in HA-treated cells. Moreover, prominent targets of the canonical Wnt signaling pathway showed reduced expression, whereas inhibitors of the pathway were considerably upregulated. We detected decrease of active β-catenin levels in HA-treated cells due to β-catenin being phosphorylated and, thus, targeted for degradation. Conclusions HA strongly induces the growth of osteoprogenitors and maintains their stemness, thus potentially regulating the balance between self-renewal and differentiation during bone regeneration following reconstructive oral surgeries. Clinical relevance Addition of HA to deficient bone or bony defects during implant or reconstructive periodontal surgeries may be a viable approach for expanding adult stem cells without losing their replicative and differentiation capabilities.

scholarly journals Surgical treatment of comminuted intraarticular distal femur fracture in patient with osteogenesis imperfecta type I

2019 ◽  
Vol 7 (1) ◽  
pp. 87-96
Author(s):  
Mikhail E. Burtsev ◽  
Aleksandr V. Frolov ◽  
Aleksei N. Logvinov ◽  
Dmitry O. Ilyin ◽  
Andrey V. Korolev
Keyword(s):  
Surgical Treatment ◽  
Osteogenesis Imperfecta ◽  
Distal Femur ◽  
Bone Fragility ◽  
Type I ◽  
Osteogenesis Imperfecta Type ◽  
Intraarticular Fracture ◽  
Femur Fractures ◽  
Intraarticular Fractures ◽  
Femur Diaphysis

Aim. Osteogenesis imperfecta (OI) is characterized by bone fragility and long bones deformities. Most studies are dedicated to surgical treatment of diaphyseal fractures. To our knowledge, there are no reports giving recommendations about surgical treatment of distal femur intraarticular fractures. Clinical case. We describe the surgical treatment of a 14-year-old girl with OI who had intraarticular fracture of the left distal femur and fracture of a right femur diaphysis. Surgical treatment was complicated by migration of a titanium elastic nail and impaired consolidation, which had to be fixed with a plate and led to peri-implant fracture. Results were assessed before trauma and at 1 and 2 years after trauma with Gillette Functional Assessment Questionnaire (GFAQ) and Bleck score. Discussion. During surgical treatment of comminuted intraarticular distal femur fractures in patients with OI, we had to use big cancellous screw that made implantation in an intramedullary fixator more difficult. Internal fixation with a plate in patients with OI is associated with high risks of peri-implant fracture. Conclusion. For treatment of comminuted intraarticular fracture of the distal femur, it is necessary to have large variety of internal fixators, follow the principles of absolute and relative stability, and be familiar with minimally-invasive techniques.

scholarly journals Tendon and Motor Phenotypes in the Crtap-/- Mouse Model of Recessive Osteogenesis Imperfecta

2020 ◽  
Author(s):  
Matthew W. Grol ◽  
Nele A. Haelterman ◽  
Joohyun Lim ◽  
Elda M. Munivez ◽  
Marilyn Archer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Bone Fragility ◽  
Joint Hypermobility ◽  
Motor Deficits ◽  
Motor Impairments ◽  
Matrix Gene ◽  
Severe Motor ◽  
Cross Links ◽  
Immature Cells

ABSTRACTOsteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass with bone fragility, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon/ligament dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles tendons and patellar ligaments were thinner with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar ligaments from Crtap-/- mice also had fewer progenitors with a concomitant increase in immature cells. RNA-seq analysis of Achilles tendons and patellar ligaments from 1-month Crtap-/- mice revealed dysregulation in matrix gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. Finally, a series of behavioral tests revealed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice – a phenotype that correlates with the tendon/ligament pathology.

scholarly journals SlpB Protein Enhances the Probiotic Potential of L. lactis NCDO 2118 in Colitis Mice Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Giovanna A. Belo ◽  
Bárbara F. Cordeiro ◽  
Emiliano R. Oliveira ◽  
Marina P. Braga ◽  
Sara H. da Silva ◽  
...  
Keyword(s):  
Weight Loss ◽  
Activity Index ◽  
Disease Activity Index ◽  
Fermented Food ◽  
Mice Model ◽  
Probiotic Potential ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Bowel Diseases ◽  
And Function

Bacteria used in the production of fermented food products have been investigated for their potential role as modulators of inflammation in gastrointestinal tract disorders such as inflammatory bowel diseases (IBD) that cause irreversible changes in the structure and function of gut tissues. Ulcerative colitis (UC) is the most prevalent IBD in the population of Western countries, and it is marked by symptoms such as weight loss, rectal bleeding, diarrhea, shortening of the colon, and destruction of the epithelial layer. The strain Propionibacterium freudenreichii CIRM-BIA 129 recently revealed promising immunomodulatory properties that greatly rely on surface-layer proteins (Slp), notably SlpB. We, thus, cloned the sequence encoding the SlpB protein into the pXIES-SEC expression and secretion vector, and expressed the propionibacterial protein in the lactic acid bacterium Lactococcus lactis NCDO 2118. The probiotic potential of L. lactis NCDO 2118 harboring pXIES-SEC:slpB (L. lactis-SlpB) was evaluated in a UC-mice model induced by Dextran Sulfate Sodium (DSS). During colitis induction, mice receiving L. lactis-SlpB exhibited reduced severity of colitis, with lower weight loss, lower disease activity index, limited shortening of the colon length, and reduced histopathological score, with significant differences, compared with the DSS group and the group treated with L. lactis NCDO 2118 wild-type strain. Moreover, L. lactis-SlpB administration increased the expression of genes encoding tight junction proteins zo-1, cln-1, cln-5, ocln, and muc-2 in the colon, increased IL-10 and TGF-β, and decreased IL-17, TNF-α, and IL-12 cytokines in the colon. Therefore, this work demonstrates that SlpB recombinant protein is able to increase the probiotic potential of the L. lactis strain to alleviate DSS-induced colitis in mice. This opens perspectives for the development of new approaches to enhance the probiotic potential of strains by the addition of SlpB protein.

scholarly journals Dental and craniofacial defects in the Crtap −/− mouse model of osteogenesis imperfecta type VII

2020 ◽  
Vol 249 (7) ◽  
pp. 884-897 ◽  
Author(s):  
He Xu ◽  
Sydney A. Lenhart ◽  
Emily Y. Chu ◽  
Michael B. Chavez ◽  
Helen F. Wimer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Osteogenesis Imperfecta Type ◽  
Craniofacial Defects

Bilateral retinoblastoma and osteogenesis imperfecta, a very rare association: Two cases

2020 ◽  
pp. 112067212091934
Author(s):  
Sonia De Francesco ◽  
Arianna Sgheri ◽  
Alessandro Di Maggio ◽  
Francesco Rana ◽  
Pinto Anna Maria ◽  
...  
Keyword(s):  
Case Report ◽  
Osteogenesis Imperfecta ◽  
Single Gene ◽  
Clinical Signs ◽  
Osteogenesis Imperfecta Type ◽  
Primary Role ◽  
Rare Association ◽  
Retinoblastoma Cells ◽  
Bilateral Retinoblastoma ◽  
Genes Encoding

Introduction This case report presents two patients affected by a very rare association of bilateral retinoblastoma and osteogenesis imperfecta. Case report Two Caucasian males with familial history and clinical signs of osteogenesis imperfecta came to our attention for bilateral leukocoria. The ocular fundus examination revealed bilateral retinoblastoma. Proper therapies were dispensed in order to achieve full regression. Genetic counseling was performed. Discussion The primary role of genetics in retinoblastoma pathogenesis in widely known, and different genes have been identified. Osteogenesis imperfecta is a rare connective tissue disorders, caused by mutated genes encoding for collagen. The single gene defect in osteogenesis imperfecta type VI is Serpin Family F Member 1 ( SERPINF1), a neurotrophic factor for the neuronal differentiation in retinoblastoma cells. The association of bilateral retinoblastoma and osteogenesis imperfecta could be the result of the mutation of a single gene playing a role in a hypothetical common pathway.

scholarly journals Dental behavior management of a patient with osteogenesis imperfecta type V: case report

2020 ◽  
Vol 28 (87) ◽  
Author(s):  
Danilo Cassiano Ferraz ◽  
Ana Luiza Rodrigues Ribeiro ◽  
Ronan Machado de Alcântra ◽  
Alessandra Maia de Castro ◽  
Fabiana Sodré de Oliveira ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Behavior Management ◽  
Parental Education ◽  
Bone Fractures ◽  
Pediatric Dentistry ◽  
Bone Fragility ◽  
Osteogenesis Imperfecta Type ◽  
Dental Biofilm ◽  
Stabilization Technique ◽  
Type V

Aim: the aim of this study is to report a case of a four-year-old male patient diagnosed with Osteogenesis Imperfecta (OI) type V and the dental care performed.  Material and method: the patient has been monitored by a multidisciplinary team composed by Pediatric Dentistry, Nurse and Nutritionist at a Special Patients Center in Dentistry Hospital on the Federal University of Uberlândia since one month of life. It was reported that a child had already suffered several bone fractures and currently he has been using calcium carbonate, D vitamin and pamidronate. Results: the proposed intervention was dental preventive strategies by parental education, caries risk assessment and controlling the dental biofilm with professional prophylaxis. But, due to the uncooperative behavior, it was used the active protective stabilization technique and mouth opener. Conclusion: it was concluded that due to the bone fragility and the risk of fractures, it is important a careful placement of the patient on the dental chair. Also, the correct use of basic auxiliary devices and advanced techniques of behavior management were relevant.

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