A new UCLA study sheds light on the link between high cholesterol and osteoporosis and identifies a new way that the body's immune cells play a role in bone loss.
Published Aug. 20 in the journal Clinical Immunology, the research could lead to new immune-based approaches for treating osteoporosis. Affecting 10 million Americans, the disease causes fragile bones and increases the risk of fractures, resulting in lost independence and mobility.
Scientists have long recognized the relationship between high cholesterol and osteoporosis, but pinpointing the exact mechanism connecting the two has proved elusive.
"We've known that osteoporosis patients have higher cholesterol levels, more severe clogging of the heart arteries and increased risk of stroke. We also knew that drugs that lower cholesterol reduce bone fractures, too," explained Rita Effros, professor of pathology at the David Geffen School of Medicine at UCLA. "What we didn't understand was why."
Effros suspected a clue to the mystery involved oxidation -- cell and tissue damage resulting from exposure of the fatty acids in cholesterol to molecules known as free radicals.
In the study, UCLA researchers focused on low-density lipoprotein (LDL), the so-called "bad" cholesterol. They examined how high levels of oxidized LDL affect bone and whether a type of immune cell called a T cell plays a role in the process.
Using blood samples from healthy human volunteers, the team isolated the participants' T cells and cultured them in a dish.
Half of the T cells were combined with normal LDL– the rest was combined with oxidized LDL. The scientists stimulated half of the T cells to mimic an immune response and left the other half alone.
"Lo and behold, both the resting and the activated T cells started churning out a chemical that stimulates cells whose sole purpose is to destroy bone," said Effros. Called RANKL, the chemical is involved in immune response and bone physiology.
To investigate further how the immune system participates in bone loss, the scientists repeated the experiment in a mouse model.
Half the animals were fed a high-fat diet starting at one month of age, while the control group ate a normal diet. At 11 months, the mice on the high-fat diet showed elevated cholesterol and thinner bones.
When Effros and her colleagues tested the T cells of the mice on the high-fat diet, they discovered that the cells acted differently than those of the mice on the normal diet.
The T cells switched on the gene that produces RANKL. The chemical also appeared in the animals' bloodstream, suggesting that the cellular activity contributed to their bone loss.
"It's normal for our T cells to produce small amounts of RANKL during an immune response," explained Effros. "But when RANKL is manufactured for long periods or at the wrong time, it results in excessive bone damage."
"That's exactly what happened to the mice on the high-fat diet," she said. "The animals' high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL. This discovery revealed to us how the immune system might play an entirely new role in bone loss."
The next step will be exploring methods to control T cell response to oxidized LDL in an effort to develop immune-based approaches to prevent or slow bone loss, Effros says.
The study was funded by the National Institute on Aging, the National Institute of Allergy and Infectious Diseases and the National Heart, Lung and Blood Institute.
Effros' coauthors were Lucia Graham, Farhad Parhami, Yin Tintut, Christina Kitchen and Linda Demer, all of UCLA.
Elaine Schmidt | EurekAlert!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
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...
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...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
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...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences