GELLES Katharina

Previous University and Subject: Biomedical Sciences, University of Applied Sciences Vienna

Thesis since: February 2022

Baricitinib for the Treatment of Age-Related Osteoporosis

Osteoporosis is a frequent age-related disorder associated with an enormous economic burden. Only a small proportion of patients with osteoporosis is treated adequately which implies an urgent need to develop new treatment strategies. The pathogenesis of osteoporosis is multifactorial. Proinflammatory cytokines play an important role in this process. Baricitinib is an inhibitor of Janus kinases (JAK) that mediates cytokine signaling and is approved for the treatment of rheumatoid arthritis. Preclinical data indicate that baricitinib treatment in young animals exhibit a bone anabolic effect. Nevertheless, the effect of JAK inhibition in a model of age-related osteoporosis has not been studied.

The primary objective of this study is to test the effect of baricitinib on bone properties by microcomputed tomography (μCT) in the senescence accelerated mouse 8 (SAMP8), an established model of age-related osteoporosis. We hypothesize that baricitinib will improve bone properties in the SAMP8 mice.

Therefore, at the age of 8 months 60 female SAMP8 mice will be randomized to baricitinib or placebo treatment. After a treatment period of six weeks, bones will be assessed by μCT, histomorphometry and bone turnover markers. As secondary aims of this project, the mechanisms of the effects of baricitinib on bone metabolism will be investigated by flow cytometry, RNA sequencing and integrative data analysis using a systems biology approach. The proposed study will make a valuable contribution to define the effects of baricitinib on bone properties in a model of age-related osteoporosis.

Methods and Skills:

Western blot; immuno histochemistry; immuno fluorescence; ELISA; FACS; tissue fax

Publications:

Molcan L, Maier A, Zemančíková A, Gelles K, Török J, Zeman M, Ellinger I. Expression of melatonin receptor 1 in rat mesenteric artery and perivascular adipose tissue and vasoactive action of melatonin. Cell Mol Neurobiol 41: 1589-1598, 2021 

Kerschan-Schindl K, Skenderi K, Wahl-Figlash K, Gelles K, Föger-Samwald U, Thalmann M, Tsironi M, Szekeres T, Pietschmann P. Increased serum levels of fibroblast growth factor 23 after an ultradistance run. J Sci Med Sport 24: 297-300, 2021

Granitzer S, Ellinger I, Khan R, Gelles K, Widhalm R, Hengstschläger M, Zeisler H, Desoye G, Tupova L, Ceckova M, Salzer H, Gundacker C. In vitro function and in situ localization of Multidrug Resistance-associated Protein (MRP)1 (ABCC1) suggest a protective role against methyl mercury-induced oxidative stress in the human placenta. Arch Toxicol 94: 3799-3817, 2020

Kamper M, Mittermayer F, Cabuk R, Gelles K, Ellinger I, Hermann M. Estrogen-enhanced apical and basolateral secretion of apolipoprotein B-100 by polarized trophoblast-derived BeWo cells. Biochemie  138: 116-123, 2017

Klameth L, Rath B, Hochmaier M, Moser D, Redl M, Mungenast F, Gelles K, Ulsperger E, Zeillinger R, Hamilton G. Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance. Sci Rep 7: 5337, 2017