For osteoporosis patients unable to exercise, help may be on the way. That's because scientists have discovered precisely how mechanical stress, such as exercise, promotes new bone growth. This opens the door to entirely new therapies that can trick bones into thinking they are getting a workout. The research report describing this advance is published online in The FASEB Journal (http://www.fasebj.org).
This research provides insight into the identification of the signaling mechanisms used by primary cilia to regulate the capacity of bone cells to sense fluid flow. This crucial information could lead to the development of new drugs that cause the same benefits to the skeleton as exercise, which would be beneficial to patients with osteoporosis.
"We believe that this study takes the field an important step forward in answering a two hundred-year-old question, 'How does bone sense mechanical loads?'" said Christopher R. Jacobs, Ph.D., co-author of the study from the Department of Mechanical Engineering at Stanford University in Stanford, CA. "Ultimately, we hope that the mechanisms identified in this study can be exploited to develop novel treatments for bone loss and perhaps a large number of other diseases involving the remarkably versatile primary cilia."
The research by Jacobs and colleagues builds on existing knowledge about the role of primary cilia (hair-like organelles that line the surfaces of some cells) on fluid flow in bone cells. When bone carries weight during physical exercise, bone cells are subjected to fluid flow, which is detected by primary cilia in bone cells. To make their discovery, the scientists studied an enzyme found in bone cells called adenylyl cyclase 6 (AC6), which is compartmentalized within the primary cilia. This enzyme inactivates very quickly in response to fluid flow, which initiates a signaling cascade that ultimately leads to increased expression of bone-forming genes. Researchers exposed bone cells to fluid flow and measured the intracellular levels of cyclic AMP, a signaling molecule synthesized by AC6, and found the levels quickly decreased after a two-minute bout of fluid flow. When scientists used RNA interference to inhibit the formation of primary cilia, as well as the production of AC6, the levels did not decrease in response to fluid flow. Results suggest that the short bout of fluid flow was sufficient to increase expression of a gene important for bone formation called cyclo-oxygenase 2. This study is one of the first to suggest that primary cilia play an important role in diseases such as osteoporosis.
"It's easy for doctors to tell osteoporosis patients that they need to get a good workout a few days each week, but the reality is that many patients are too frail to do so," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This ground-breaking study details the exact biochemical signals used by bone cells to turn the daily work-out into new bone. This research pinpoints new targets for drugs that will allow physicians to break this cycle of frailty, bone loss, and incapacity, so that patients can live longer, healthier, and more active lives."
Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.
FASEB comprises 23 societies with more than 90,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve—through their research—the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Details: Ronald Y. Kwon, Sara Temiyasathit, Padmaja Tummala, Clarence C. Quah, and Christopher R. Jacobs. Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells. FASEB J. doi:10.1096/fj.09-148007 ; http://www.fasebj.org/cgi/content/abstract/fj.09-148007v1
Cody Mooneyhan | EurekAlert!
New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)
Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Earth Sciences
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy