Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now elucidated a molecular mechanism which regulates the equilibrium between bone formation and bone resorption.
Dr. Jeske J. Smink, Dr. Valérie Bégay, and Professor Achim Leutz were able to show that two different forms of a gene switch - a short isoform and a long isoform - determine this process. The MDC researchers hope these findings will lead to new therapies for this bone disease. (EMBO Journal)*.
In osteoporosis, excessive bone resorption occurs. The bones lose their density and are therefore prone to breakage. Even minor falls can lead to serious bone fractures. The interplay between two cell types determines bone density: bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts). The equilibrium between these two cell types is strictly regulated to prevent the formation of either too much or too little bone.
LAP activates another gene switch (MafB) which suppresses the formation of bone resorbing osteoclasts. In contrast, LIP, suppresses this gene switch and thus enhances the proliferation and activity of the osteoclasts. As a result, the osteoclasts resorb more bone substance than is built by the osteoblasts. The researchers suspect that imbalance in the ratio between LAP and LIP plays a role in osteoporosis.
The activity of a signaling molecule - mTOR - determines which of the two isoforms LAP and LIP is formed. The abbreviation mTOR stands for mammalian Target of Rapamycin. The drug rapamycin inhibits mTOR and thus suppresses the formation of bone resorbing osteoclasts. Unfortunately, rapamycin has severe side-effects on the immune system. "In the future, it may be possible to develop new drugs that regulate the activity of mTOR and, thus, remedy the disturbance in osteoclast function," Professor Leutz said.
*Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB
Jeske J. Smink1,4, Valérie Bégay1,4, Ton Schoenmaker2, Esta Sterneck3, Teun J. de Vries2, and Achim Leutz11 Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
4 these authors contributed equally to this workBarbara Bachtler
Barbara Bachtler | Max-Delbrück-Centrum
Scientists decipher key principle behind reaction of metalloenzymes
15.01.2018 | Rheinisch-Westfälische Technische Hochschule Aachen
New method to map miniature brain circuits
15.01.2018 | The Francis Crick Institute
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
Scientists at Helmholtz Zentrum München have discovered a mechanism that amplifies the autoimmune reaction in an early stage of pancreatic islet autoimmunity prior to the progression to clinical type 1 diabetes. If the researchers blocked the corresponding molecules, the immune system was significantly less active. The study was conducted under the auspices of the German Center for Diabetes Research (DZD) and was published in the journal ‘Science Translational Medicine’.
Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the...
15.01.2018 | Event News
08.01.2018 | Event News
11.12.2017 | Event News
15.01.2018 | Physics and Astronomy
15.01.2018 | Life Sciences
15.01.2018 | Life Sciences