@article{OhlebuschBorstFrankenbachetal.2020,
  author    = {Ohlebusch, Barbara and Borst, Angela and Frankenbach, Tina and Klopocki, Eva and Jakob, Franz and Liedtke, Daniel and Graser, Stephanie},
  title     = {Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-70152-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230024},
  year      = {2020},
  abstract  = {Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.},
  language  = {en}
}
@article{EbertBenischKrugetal.2015,
  author    = {Ebert, Regina and Benisch, Peggy and Krug, Melanie and Zeck, Sabine and Meißner-Weigl, Jutta and Steinert, Andre and Rauner, Martina and Hofbauer, Lorenz and Jakob, Franz},
  title     = {Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells},
  series = {Stem Cell Research},
  volume    = {15},
  journal   = {Stem Cell Research},
  doi       = {10.1016/j.scr.2015.06.008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148491},
  pages     = {231-239},
  year      = {2015},
  abstract  = {The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.},
  language  = {en}
}