Effects of nutrition and obesity on bone health

Contact persons: Prof. Dr. Tim J. Schulz, Dr. George Soultoukis
Team: Marina Leer, Theresa Charlotte Rinne, Dr. George Soultoukis, Nicole Dittberner
Funding: DFG

Identification and isolation of bone marrow-resident adipocytes (a) Hematoxylin and eosin staining for microscopic assessment of bone marrow adipocytes. Pink areas: compact bone; dark purple areas: bone marrow; white circular areas (black arrows): adipocytes. (b) Immunofluorescence staining of marrow adipocytes by detection of adipocyte marker perilipin on adipocyte surfaces (red circular structures indicated by white arrows: anti-perilipin staining) within the marrow cavity (blue: DAPI staining of cell nuclei). Compact bone is marked with broken white lines. (c) Flow cytometric analysis of boneresident cell populations by selection of surface proteins that specifically label adipogenic progenitor cells (red arrow, upper left quadrant). (d) Oil Red O staining of isolated progenitors shows their ability to undergo differentiation into mature lipid-containing adipocytes.

Diseases of the musculoskeletal system are among the most common causes of clinical treatment and can significantly reduce the quality of life of those affected. Especially in old age, fractures and the loss of healthy bone mass, osteoporosis, increase.

In order to enable sustained health-span throughout life, it is necessary to identify the molecular causes that contribute to the development of age-related degenerative diseases in order to create a basis for innovative therapeutic approaches. In our studies to date, we have been able to show that an excessive accumulation of adipocytes in the bone marrow cavity inhibits blood formation from the bone marrow (hematopoiesis) and bone healing (osteogenesis). Accordingly, in aged mice, which were additionally fed a high-fat diet, there was an increased accumulation of adipose tissue in the bones. This finding can be seen as an indication that the diet, in connection with increasing age, is an important factor in the development of pathological processes in the bone and can contribute to bone loss and impaired fracture healing (Ambrosi et al, Cell Stem Cell 2017).

We are currently investigating the cell biology and nutrition-based mechanisms of these processes. The disruption of bone healing is based on a changed commitment of multipotent stem cells towards an adipogenic developmental lineage at the expense of normal osteogenic specialization. For our analyses at stem cell level, we employ cutting-edge methods of single cell analysis to investigate the influence of nutrition on the genetic and epigenetic regulatory mechanisms of stem cell function. In addition, the effects of various nutritional components on bone health are determined with the help of dietary intervention experiments in animal models. Based on these findings, we aim to determine to what extent nutrition can favorably influence therapeutic approaches that improve bone health.

In addition to the nutrition-based trials, pharmacological approaches are also pursued. For example, we have previously linked a group of drugs known from diabetes therapy, the Gliptins, to improved bone healing. In addition to their positive effects on glucose metabolism, Gliptins reduce the pathological effects of adipocytes in the bone (Ambrosi et al, Cell Stem Cell 2017). The goal of future studies will therefore be to evaluate this group of drugs with regard to their possible uses in patients with impaired bone healing, for example in old age or with obesity.