Kornak, Uwe

[["dc.bibliographiccitation.firstpage","277"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.lastpage","284"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Koehne, Till"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Lehmann, Wolfgang"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","Oheim, Ralf"],["dc.date.accessioned","2018-11-07T10:27:44Z"],["dc.date.available","2018-11-07T10:27:44Z"],["dc.date.issued","2017"],["dc.description.abstract","Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome that involves an osteopetrosis-like sclerosis of the long bones and fibrous dysplasia-like cemento-osseous lesions of the jawbone. Although the genetic analysis of the respective patients has revealed mutations in the ANO5 gene as an underlying cause, there is still no established consensus regarding the bone status of GDD patients. We report a new case of GDD in a 13-year-old boy with recurrent diaphyseal fractures of the femur, in whom we identified a novel de novo missense mutation in the ANO5 gene, causing a p.Ser500Phe substitution at the protein level. After confirming the presence of GDD-characteristic abnormalities within the jaw bones, we focused on a full osteologic assessment using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses. We thereby identified increased trabecular bone mass accompanied by elevated serum markers of bone formation and bone resorption. The high turnover bone pathology was further confirmed through the analysis of an iliac crest biopsy, where osteoblast and osteoclast indices were remarkably increased. Taken together, our findings provide evidence for a critical and generalized role of anoctamin-5 (the protein encoded by the ANO5 gene) in skeletal biology. As it is reasonable to speculate that modifying the function of anoctamin-5 might be useful for therapeutically activating bone remodeling, it is now required to analyze its function at a molecular level, for instance in mouse models. (C) 2016 American Society for Bone and Mineral Research."],["dc.identifier.doi","10.1002/jbmr.2980"],["dc.identifier.isi","000396935300011"],["dc.identifier.pmid","27541832"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43288"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1523-4681"],["dc.relation.issn","0884-0431"],["dc.title","A Novel ANO5 Mutation Causing Gnathodiaphyseal Dysplasia With High Bone Turnover Osteosclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Krawitz, Peter"],["dc.contributor.author","Zemojtel, Tomasz"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Robinson, Peter"],["dc.date.accessioned","2020-06-19T09:54:53Z"],["dc.date.available","2020-06-19T09:54:53Z"],["dc.date.issued","2014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66546"],["dc.title","Gene Panel Diagnostics for Disorders with Abnormal Bone Mass: Results From 50 Patients"],["dc.type","report"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Howaldt, Antonia"],["dc.contributor.author","Hennig, Anna"],["dc.contributor.author","Stelzer, Nina"],["dc.contributor.author","Böttger, Sebastian"],["dc.contributor.author","Zustin, Jozef"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Geissler, Sven"],["dc.contributor.author","Howaldt, Hans-Peter"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2020-06-19T10:10:18Z"],["dc.date.available","2020-06-19T10:10:18Z"],["dc.date.issued","2019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66560"],["dc.title","Osteopetrosis leading to subtotal loss of the viscerocranial bones"],["dc.type","report"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.contributor.author","Stürznickel, Julian"],["dc.contributor.author","Jähn‐Rickert, Katharina"],["dc.contributor.author","Zustin, Jozef"],["dc.contributor.author","Hennig, Floriane"],["dc.contributor.author","Delsmann, Maximilian M."],["dc.contributor.author","Schoner, Katharina"],["dc.contributor.author","Rehder, Helga"],["dc.contributor.author","Kreczy, Alfons"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Oheim, Ralf"],["dc.date.accessioned","2021-04-14T08:29:25Z"],["dc.date.available","2021-04-14T08:29:25Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1002/jbmr.4277"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82893"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1523-4681"],["dc.relation.issn","0884-0431"],["dc.title","Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","100281"],["dc.bibliographiccitation.journal","Bone Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Avci, Osman"],["dc.contributor.author","von Kroge, Simon"],["dc.contributor.author","Koehne, Till"],["dc.contributor.author","Selbert, Stefan"],["dc.contributor.author","Sonntag, Stephan"],["dc.contributor.author","Shmerling, Doron"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","Yorgan, Timur Alexander"],["dc.date.accessioned","2020-06-23T10:10:28Z"],["dc.date.available","2020-06-23T10:10:28Z"],["dc.date.issued","2020-06"],["dc.description.abstract","Mutations in the gene ANO5, encoding for the transmembrane protein Anoctamin 5 (Ano5), have been identified to cause gnathodiaphyseal dysplasia (GDD) in humans, a skeletal disorder characterized by sclerosis of tubular bones, increased fracture risk and fibro-osseous lesions of the jawbones. To better understand the pathomechanism of GDD we have generated via Crispr/CAS9 gene editing a mouse model harboring the murine equivalent (Ano5 p.T491F) of a GDD-causing ANO5 mutation identified in a previously reported patient. Skeletal phenotyping by contact radiography, μCT and undecalcified histomorphometry was performed in male mice, heterozygous and homozygous for the mutation, at the ages of 12 and 24 weeks. These mice did not display alterations of skeletal microarchitecture or mandible morphology. The results were confirmed in female mice and animals derived from a second, independent clone. Finally, no skeletal phenotype was observed in mice lacking ~40% of their Ano5 gene due to a frameshift mutation. Therefore, our results indicate that Ano5 is dispensable for bone homeostasis in mice, at least under unchallenged conditions, and that these animals may not present the most adequate model to study the physiological role of Anoctamin 5."],["dc.identifier.doi","10.1016/j.bonr.2020.100281"],["dc.identifier.pmid","32455153"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66657"],["dc.language.iso","en"],["dc.relation.issn","2352-1872"],["dc.title","Gnathodiaphyseal dysplasia is not recapitulated in a respective mouse model carrying a mutation of the Ano5 gene"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","eaau7137"],["dc.bibliographiccitation.issue","466"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Luther, Julia"],["dc.contributor.author","Yorgan, Timur Alexander"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Ulsamer, Lorenz"],["dc.contributor.author","Koehne, Till"],["dc.contributor.author","Liao, Nannan"],["dc.contributor.author","Keller, Daniela"],["dc.contributor.author","Vollersen, Nele"],["dc.contributor.author","Teufel, Stefan"],["dc.contributor.author","Neven, Mona"],["dc.contributor.author","Peters, Stephanie"],["dc.contributor.author","Schweizer, Michaela"],["dc.contributor.author","Trumpp, Andreas"],["dc.contributor.author","Rosigkeit, Sebastian"],["dc.contributor.author","Bockamp, Ernesto"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","David, Jean-Pierre"],["dc.date.accessioned","2020-06-24T12:52:57Z"],["dc.date.available","2020-06-24T12:52:57Z"],["dc.date.issued","2018"],["dc.description.abstract","WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis."],["dc.identifier.doi","10.1126/scitranslmed.aau7137"],["dc.identifier.pmid","30404864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66718"],["dc.language.iso","en"],["dc.relation.eissn","1946-6242"],["dc.relation.issn","1946-6234"],["dc.title","Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.contributor.author","Howaldt, Antonia"],["dc.contributor.author","Hennig, Anna Floriane"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Rössler, Uta"],["dc.contributor.author","Stelzer, Nina"],["dc.contributor.author","Knaus, Alexej"],["dc.contributor.author","Böttger, Sebastian"],["dc.contributor.author","Zustin, Jozef"],["dc.contributor.author","Geißler, Sven"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Howaldt, Hans-Peter"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2020-06-23T09:43:35Z"],["dc.date.available","2020-06-23T09:43:35Z"],["dc.date.issued","2020-03-02"],["dc.description.abstract","Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs 33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research."],["dc.identifier.doi","10.1002/jbmr.3995"],["dc.identifier.pmid","32119750"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66627"],["dc.language.iso","en"],["dc.relation.eissn","1523-4681"],["dc.relation.issn","0884-0431"],["dc.title","Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","271"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.lastpage","282"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Stürznickel, Julian"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Delsmann, Alena"],["dc.contributor.author","Butscheidt, Sebastian"],["dc.contributor.author","Barvencik, Florian"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Oheim, Ralf"],["dc.date.accessioned","2021-04-14T08:32:19Z"],["dc.date.available","2021-04-14T08:32:19Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/jbmr.4197"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83880"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1523-4681"],["dc.relation.issn","0884-0431"],["dc.title","Clinical Phenotype and Relevance of LRP5 and LRP6 Variants in Patients With Early‐Onset Osteoporosis ( EOOP )"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","512"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Calcified Tissue International"],["dc.bibliographiccitation.lastpage","521"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Stürznickel, Julian"],["dc.contributor.author","Schmidt, Felix N"],["dc.contributor.author","Butscheidt, Sebastian"],["dc.contributor.author","Schmidt, Tobias"],["dc.contributor.author","Busse, Björn"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Schinke, Thorsten"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Oheim, Ralf"],["dc.date.accessioned","2020-06-23T09:44:11Z"],["dc.date.available","2020-06-23T09:44:11Z"],["dc.date.issued","2018"],["dc.description.abstract","Diagnosis and management of adult individuals with low bone mass and increased bone fragility before the age of 50 can be challenging. A number of these patients are diagnosed with mild osteogenesis imperfecta (OI) through detection of COL1A1 or COL1A2 mutations; however, a clinical differentiation from early-onset osteoporosis (EOOP) may be difficult. The purpose of this study was to determine the bone microstructural differences between mild OI and EOOP patients. 29 patients showed mutations in COL1A1 or COL1A2 and were classified as OI. Skeletal assessment included dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone turnover serum analyses. Bone microstructure of 21/29 OI patients was assessed and compared to 23 age- and sex-matched patients clinically classified EOOP but without mutations in the known disease genes as well as to 20 healthy controls. In the OI patients, we did not observe an age-dependent decrease in DXA Z-scores. HR-pQCT revealed a significant reduction in volumetric BMD and microstructural parameters in the distal radius and tibia in both the OI and EOOP cohorts compared to the healthy controls. When comparing the bone microstructure of OI patients with the EOOP cohort, significant differences were found in terms of bone geometry in the radius, while no significant changes were detected in all other HR-pQCT parameters at the radius and tibia. Taken together, adult mild OI patients demonstrate a predominantly high bone turnover trabecular bone loss syndrome that shows minor microstructural differences compared to EOOP without mutation detection."],["dc.identifier.doi","10.1007/s00223-018-0447-8"],["dc.identifier.pmid","29946973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66633"],["dc.language.iso","en"],["dc.relation.eissn","1432-0827"],["dc.relation.issn","0171-967X"],["dc.title","Comparison of Bone Microarchitecture Between Adult Osteogenesis Imperfecta and Early-Onset Osteoporosis"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","115062"],["dc.bibliographiccitation.journal","Bone"],["dc.bibliographiccitation.volume","130"],["dc.contributor.author","Yorgan, Timur Alexander"],["dc.contributor.author","Sari, Hatice"],["dc.contributor.author","Rolvien, Tim"],["dc.contributor.author","Windhorst, Sabine"],["dc.contributor.author","Failla, Antonio Virgilio"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Oheim, Ralf"],["dc.contributor.author","Amling, Michael"],["dc.contributor.author","Schinke, Thorsten"],["dc.date.accessioned","2020-06-23T10:10:14Z"],["dc.date.available","2020-06-23T10:10:14Z"],["dc.date.issued","2020-01"],["dc.description.abstract","Although inactivating mutations of PLS3, encoding the actin-bundling protein plastin-3, have been identified to cause X-linked osteoporosis, the cellular and molecular influence of PLS3 on bone remodeling is poorly defined. Moreover, although a previous study has demonstrated moderate osteopenia in 12 week-old Pls3-deficient mice based on μCT scanning, there is no reported analysis of such a model on the basis of undecalcified histology and bone-specific histomorphometry. To fill this knowledge gap we applied a deep phenotyping approach and studied Pls3-deficient mice at different ages. Surprisingly, we did not detect significant differences between wildtype and Pls3-deficient littermates with respect to trabecular bone mass, and the same was the case for all histomorphometric parameters determined at 12 weeks of age. Remarkably however, the cortical thickness in both, tibia and femur, was significantly reduced in Pls3-deficient mice in all age groups. We additionally studied the ex vivo behavior of Pls3-deficient primary osteoblasts, which displayed moderately impaired mineralization capacity. Of note, while most osteoblastogenesis markers were not differentially expressed between wildtype and Pls3-deficient cultures, the expression of Sfrp4 was significantly reduced in the latter, a potentially relevant finding, since Sfrp4 inactivation, in mice and humans, specifically causes cortical thinning. We finally addressed the question, if Pls3-deficiency would impair the osteoanabolic influence of parathyroid hormone (PTH). For this purpose we applied daily injection of PTH into wildtype and Pls3-deficient mice and found a similar response regardless of the genotype. Taken together, our data reveal that Pls3-deficiency in mice only recapitulates the cortical bone phenotype of individuals with X-linked osteoporosis by negatively affecting the early stage of cortical bone acquisition."],["dc.identifier.doi","10.1016/j.bone.2019.115062"],["dc.identifier.pmid","31678489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66654"],["dc.language.iso","en"],["dc.relation.eissn","1873-2763"],["dc.relation.issn","8756-3282"],["dc.title","Mice lacking plastin-3 display a specific defect of cortical bone acquisition"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]