Metabolism and Bone
How Metabolic Diseases Control Bone
In the Bone Lab, we are mainly focusing on two metabolic/endocrine diseases: obesity/diabetes and thyroid dysfunction.
Bone in patients with diabetes breaks easily and heals poorly. For the patients, this means immobility over months and as a consequence less life quality. Type 2 diabetes mellitus and osteoporosis may affect half of the aging European population. However, the ‘sweet bone phenomenon’ remains a conundrum, since bone mineral density is paradoxically high or normal. Therefore, we set out to answer the fundamental question “How is bone weakened by diabetes?”
We believe that bone material strength is affected by direct and indirect effects of type 2 diabetes mellitus on bone. In the last years, our group has found that bone microarchitecture and accumulation of advanced glycosation endproducts (AGE) contribute to poor bone quality in diabetes. In our ongoing studies, we test how microvascular damage may contribute to impaired bone cell function. To tackle these research questions, we use preclinical models and comprehensively assess intact and regenerating bone with a spectrum of high-resolution imaging modalities and advanced cell biology methods.
Thyroid hormones control growth, shape, and accrual of bone. They are indispensable for normal bone development and homeostasis. As undiagnosed hyperthyroidism is an important risk factor for falls and osteoporotic fractures, we see a need to uncover mechanisms of bone loss associated with altered thyroid function that may translate into better bone health.
In this area, we define how thyroid hormones and their receptors affect bone biology and skeletal strength with a focus on osteocyte biology. Recent work from our group shows that osteocytes in hyperthyroid bone acquire osteoclast-like features, and that loss of thyroid hormone receptor α (TRα) protects against hyperthyroidism-driven cortical bone loss by limiting bone resorption. Moreover, we are interested in how thyroid hormones enter bone cells to exert their function. Using murine transgenic models as well as pharmacological-induced models of hyperthyroidism we aim to decipher underlying mechanisms of disease and contribute to the development of tailored individualized therapies.
Principal Investigators
Franziska Brinkmann, PhD
«Science isn´t about why… it is about why not.»
Elena Tsourdi, MD
«The molecular mechanisms underlying the distinct bone phenotypes caused by thyroid dysfunction are largely unknown-even more the challenge to try to unravel them!»
Martina Rauner, PhD
«The impact of thyroid hormones on bone is extremly strong. I have rarely seen such a high bone turnover as in mice with hyperthyroidism»
Lorenz Hofbauer, MD
«Small hormones, big impact.»
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- Stephanie Zeiler
Research Question
Thyroid hormones control the activity of many body functions, including the skeleton. Their effects vary greatly between people and even within a person, some organs may be more susceptible than others. What determines thyroid hormones responsiveness in bone and which determinants control it.
Approach
We use preclinical models rendered hyperthyroid, knock-out and transgenic models to mimic a gradient of systemic or tissue specific excess or deficiency of thyroid hormones. This allows defining the spectrum of effects of an altered thyroid function on the skeleton.
Projects
- Impact of mTORC1 on thyroid hormone action on bone and bone cell metabolism
- Effects of thyroid hormone receptor knockout on bone cell physiology
- Implications of thyroid hormones and their receptors in bone defect healing
- Impact of obesity/diabetes and bone marrow adipose tissue
Funding
Funded by the DFG as well as by the Elsbeth Bonhoff-Stiftung and the Fritz Thyssen-Stiftung.
