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Studying bone marrow adiposity in different mouse models of obesity and osteoporosis

Laboratory namet: Molecular Physiology of Bone

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PhD project: Studying bone marrow adiposity in different mouse models of obesity and osteoporosis

Obesity and osteoporosis are metabolic bone diseases accompanied with higher accumulation of bone marrow adipose tissue (BMAT) associated with increased risk of bone fractures and bone loss. However, it is still not well documented how bone marrow adiposity affects bone microstructure and bone properties in these pathophysiological conditions. Thus, the aim of this project using different mouse models of obesity (B6, A/J mice and transgenic mice) and osteoporosis (ovariectomized (OVX) mice), is to investigate BMAT distribution and its molecular properties in different skeleton site in relation to bone quality in animal models of metabolic bone diseases.

The project will employ in vivo phenotyping techniques (analyzing bone microstructure using different bioimaging methods microCT, contrast-enhanced CT, and specific program analysis), working with animal models applying several molecular, bioanalytical methods. Project will be conducted at the Institute of Physiology of CAS in collaboration with excellent laboratories abroad. The basic PhD scholarship will be supported by the Czech Science Foundation.

 

Relevant publications:

-Benova A., et al. Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones. Mol Metab. 2022 Nov;65:101598. doi: 10.1016/j.molmet.2022.101598. Epub 2022 Sep 11

-Tencerova M, et al. Metabolic programming of bone marrow stromal stem cells determines lineage- differentiation fate. Bone Res. 2019 Nov 14;7:35. doi: 10.1038/s41413-019-0076-5.

-Tencerova M, et al. Obesity associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 2019 May 14;27(7):2050-2062.e6. doi: 10.1016/j.celrep.2019.04.066.

-Tencerova M, et al. High fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J Bone Miner Res. 2018 Feb 14. doi: 10.1002/jbmr.3408.

- Tencerova M, Kassem M. The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis. Front Endocrinol (Lausanne). 2016 Sep 21;7:127.

 

Supervisor: Michaela Tencerova, Ph.D. (Michaela.Tencerova@fgu.cas.cz)

 

Candidate’s profile (requirements): We are seeking highly motivated, creative candidates with MSc degree or equivalent in molecular biology, biochemistry, physiology, medicine, pharmacology or related disciplines, or students expecting to obtain their degree this year. Experience with molecular biology techniques and in vitro cell culture methods are advantage.