29.1. 2024, Molekulární fyziologie kosti

PhD project:
Studying bone marrow adiposity in mouse models of obesity: impact of sex dimorphism

Obesity is a metabolic bone disease accompanied with higher accumulation of bone marrow adipose tissue (BMAT) associated with increased risk of bone fractures and bone loss. With obesity, the function of key building blocks, bone marrow stromal cells (BMSCs) changes towards higher accumulation of BMAT, which is affected by diet and sex dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes across the life span, which may contribute to different prevalence of bone fractures among men and women. However, the exact molecular mechanism behind the sex-related differences in pathophysiology of bone are not well known. Thus, the aim of this project using different mouse models of obesity (B6, A/J mice and transgenic mice), is to investigate the impact of different diet interventions on BMAT expansion and BMSC molecular properties in relation to bone quality with respect to sex dimorphism.The project will employ in vivo phenotyping techniques (analyzing metabolic parameters, bone microstructure using different bioimaging methods microCT, contrast-enhanced CT, and specific program analysis), working with animal models, isolation of primary BMSC and 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 national grants.

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.

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)