Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing

17.03.2017

A new study led by the German Institute of Human Nutrition (DIfE), a partner of the German Center for Diabetes Research (DZD), shows that gliptins – well known from diabetes treatment – may oppose the detrimental effects of fat cell accumulation in the bone marrow to improve bone healing in older, overweight patients. The research team led by stem cell researchers Thomas H. Ambrosi and Tim J. Schulz has now published its findings in Cell Stem Cell (Ambrosi et al. 2017; http://dx.doi.org/10.1016/j.stem.2017.02.009).

It is well established that aging promotes the development of obesity. The aging process is not only accompanied by larger fat depots but also by excessive atypical fat cell accumulation in other tissue types, for example in bone marrow. As recent studies suggest, such changes are associated with loss of bone mass (osteoporosis), increased risk of bone fractures, and a disturbed maturation of the immune and blood cells in the bone marrow.


A large number of preadipocytes can be identified or analyzed by the FACS® (Fluorescence Activated Cell Sorting) analysis.

Till Budde/DIfE

In addition, other studies show that people with type 2 diabetes are particularly prone to bone fractures. The biological mechanisms underlying these observations have not been sufficiently investigated. In the present study the scientists investigated the cellular and molecular causes of these processes using cell culture experiments and studies on mice.

As the researchers show for the first time, a high-fat diet, especially in combination with an advanced age, leads to an increase of specialized (adipogenic) progenitor cells in the bone marrow, which ultimately contribute to adipocyte accumulation in the bone. Excessive bone fat not only impairs bone healing, but also hampers blood cell formation in the bone marrow of the long bones. In addition, the scientists observed that bone cell development is impaired in old age.

“Our investigations thus confirm the observations of previous studies and may explain why bone fractures do not heal as well in old age, especially if the patients are overweight due to a high-fat diet," says first author Ambrosi. “We identified a potential molecular link that mediates the negative effect of fat cells on bone tissue regeneration, the protein-cleaving enzyme dipeptidyl peptidase 4, better known as DPP4," adds Schulz, who led the study.

This enzyme is already well known in diabetes research because it degrades hormones that regulate glucose metabolism. Its activity promotes high blood glucose levels and impairs the function of the insulin-producing cells of the pancreas. Based on these findings, pharmaceutical companies have developed various drugs, the so-called gliptins or DPP4 inhibitors, which – taken as a tablet – reduce the negative influence of DPP4 on the blood sugar level.

“Our discovery that DPP4, in addition to its influence on glucose metabolism, plays an important role in the cellular composition of bones is particularly interesting with regard to observations that people with type 2 diabetes have a tendency to sustain bone fractures," says Ambrosi. “It points to a direct relationship between metabolic disorders and fracture susceptibility,” the scientist continues.

“It also provides a novel therapeutic approach to improve the regenerative capacity of the bones by means of drugs, particularly in elderly and overweight people. It is a particular advantage that DPP4 inhibitors have been used in diabetes therapies for many years,” adds Schulz, who heads the Department of Adipocyte Development and Nutrition at the DIfE. Both agree that further research will be necessary with respect to the treatment of bone fractures using gliptins.

In addition to these investigations with immediate medical relevance, the researchers show in extensive cell-biological studies that the composition of the diet directly affects the stem cells of the bone and determines whether they form bone or adipogenic progenitor cells*. In future studies, the scientists aim to investigate how specific diets and food components can be used to support bone healing. However, the results of the study already show that people can do a lot for their bone health by following a balanced diet and by maintaining a healthy body weight, according to Schulz and Ambrosi.

In addition to DIfE/DZD scientists, the study also included researchers from the Wellcome Trust Sanger Institute and the European Bioinformatics Institute in the UK, the Monell Chemical Senses Center in the USA, the Sidra Medical and Research Center in Qatar, and Charité – Universitätsmedizin Berlin.

Background Information:

* Stem cells are generally defined as body cells which can transform (differentiate) into different cell types or tissues. Depending on the type of stem cell, they have the potential to develop into any tissue of the body (embryonic stem cells) or are more limited to certain tissue types (adult stem cells). Stem cells are able to divide asymmetrically, that is, to generate two different daughter cells. One daughter cell possesses stem cell properties; this is referred to as the ability of the stem cell for self-renewal.

The second daughter cell is characterized by a greater degree of differentiation and is also referred to as a progenitor cell for a particular tissue type, for example a bone or adipogenic progenitor cell. A mechanism that has not yet been elucidated in every detail enables this asymmetric division step. The respective biological micro-environment in which they reside determines the fate of the cells, which also refers to the availability of certain nutrients or hormones, among other things.

Bone marrow contains two different adult stem cells from which on the one hand precursors for bones, fat and cartilage develop. On the other hand, it also contains stem cells from which the various blood cells, i.e. the red and white blood cells, can develop.

Publication: Ambrosi, T.H.; Scialdone, A.; Graja, A.; Gohlke, S.; Jank, A.-M.; Bocian, C.; Woelk, L.; Fan, H.; Logan, W.D.; Schürmann, A.; Saraiva, L.R.; Schulz, T.J.: Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell, http://dx.doi.org/10.1016/j.stem.2017.02.009 (2017)

The German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) is a member of the Leibniz Association. It investigates the causes of diet-related diseases in order to develop new strategies for prevention and therapy and to provide dietary recommendations. Its research focus includes the causes and consequences of the metabolic syndrome, which is a combination of obesity, high blood pressure, insulin resistance and lipid metabolism disorder, as well as the role of diet in healthy aging and the biological basis of food choices and eating habits. More information at www.dife.de. In addition, the DIfE is a partner of the German Center for Diabetes Research (DZD), which was founded in 2009 and has since been funded by the BMBF. More information on the DZD can be found at https://www.dzd-ev.de/en/index.html.

The Leibniz Association is the umbrella organization for 91 independent research institutions whose spectrum encompasses the natural, engineering and environmental sciences, economics, the spatial and social sciences as well as the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, also in the overarching Leibniz research networks; they comprise and maintain scientific infrastructure and provide research-based services. The Leibniz Association sets priorities in knowledge transfer, in particular with the Leibniz research museums. It provides advice and information for policymakers, academia, business and industry, and the general public. Leibniz institutions maintain close cooperative relationships with universities – inter alia in the form of “Leibniz Science Campi”, as well as with industry and other partners in Germany and abroad. They are subject to a transparent and independent evaluation procedure. Due to the importance of the Leibniz Institutes for Germany as a whole, they are funded jointly by the federal government and state governments, employing some 18,600 individuals, including 9,500 researchers. The overall budget of the institutes amounts to more than EUR 1.7 billion. More information is available at https://www.leibniz-gemeinschaft.de/en/home/.

Weitere Informationen:

http://www.dife.de/forschung/abteilungen/kurzprofil.php?abt=ADE&lang=en Department of Adipocyte Development and Nutrition

Dr. Gisela Olias | idw - Informationsdienst Wissenschaft

Further reports about: DIfE Diabetes Drug Ernährungsforschung blood cells bone fractures stem cells

More articles from Studies and Analyses:

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

nachricht Pan-European study on “Smart Engineering”
30.03.2017 | IPH - Institut für Integrierte Produktion Hannover gGmbH

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>