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
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences