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Stem cell transplantation may correct rare genetic disorder in kids

September 19, 2009 By admin Leave a Comment

Washington, Sep 18 (ANI): Scripps Research Institute scientists have offered new hope for parents whose children suffer from the rare genetic disorder ‘cystinosis’ by showing through an experiment on mice that stem cell transplantation can successfully correct the defect.

“After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder. This study is an important step toward that goal,” said principal investigator Stephanie Cherqui.

In the study, the researchers used bone marrow stem cell transplantation to address symptoms of cystinosis in a mouse model.

The procedure virtually halted the cystine accumulation responsible for the disease, and the cascade of cell death that follows.

Cystine is a by-product of the break down of cellular components the body no longer needs in the cell’s “housekeeping” organelles, called lysosomes.

Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes it to build up, forming crystals that are especially damaging to the kidneys and eyes.

Cystinosis is a rare but devastating disease affecting children as young as six months, who begin to suffer renal dysfunction, which grows progressively worse with time. Other symptoms include diabetes, muscular disease, neurological dysfunction, and retinopathy.

The only available drug to treat cystinosis, cysteamine, while slowing the progression of kidney degradation, does not prevent it, and end-stage kidney failure is inevitable.

In the new study, the researchers found that transplanted bone marrow stem cells carrying the normal lysosomal cystine transporter gene abundantly engrafted into every tissue of the experimental mice.

This led to an average drop in cystine levels of about 80 percent in every organ.

Not only it prevented kidney dysfunction, there was less deposition of cystine crystals in the cornea, less bone demineralization, and an improvement in motor function.

“The results really surprised and encouraged us. Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective,” says Cherqui.

Cherqui said that adult bone marrow stem cell therapy is particularly well suited as a potential treatment for cystinosis because these cells target all types of tissues.

In addition, stem cells reside in the bone marrow for the duration of a patient’s life, becoming active as needed, a particular benefit for a progressive disease like cystinosis.

The study has been published in the journal Blood. (ANI)

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Scientists identify ‘tipping points’ at which sudden shifts to new conditions occur

September 3, 2009 By admin Leave a Comment

Washington, September 3 (ANI): In a new research, scientists have identified ‘tipping points’ at which sudden shifts to new conditions occur in the world.

The research was done by Martin Scheffer of Wageningen University in The Netherlands and co-authors, including William Brock and Stephen Carpenter of the University of Wisconsin at Madison and George Sugihara of the Scripps Institution of Oceanography in La Jolla, California.

They found that abrupt changes in ocean circulation and Earth’s climate, shifts in wildlife populations and ecosystems, the global finance market and its system-wide crashes, and asthma attacks and epileptic seizures share generic early-warning signals that indicate a critical threshold of change dead ahead.

The team found that similar symptoms occur in many systems as they approach a critical state of transition.

“It’s increasingly clear that many complex systems have critical thresholds – ‘tipping points’ – at which these systems shift abruptly from one state to another,” according to the scientists.

Especially relevant, they discovered, is that “catastrophic bifurcations,” a diverging of the ways, propel a system toward a new state once a certain threshold is exceeded.

A system follows a trail for so long, then often comes to a switchpoint at which it will strike out in a completely new direction.

That system may be as tiny as the alveoli in human lungs or as large as global climate.

“These are compelling insights into the transitions in human and natural systems,” said Henry Gholz, program director in the National Science Foundation (NSF)’s Division of Environmental Biology, which supported the research along with NSF’s Division of Ocean Sciences.

“The information comes at a critical time – a time when Earth’s and, our fragility, have been highlighted by global financial collapses, debates over health care reform, and concern about rapid change in climate and ecological systems,” he added.

It all comes down to what scientists call “squealing,” or “variance amplification near critical points,” when a system moves back and forth between two states.

“A system may shift permanently to an altered state if an underlying slow change in conditions persists, moving it to a new situation,” said Carpenter.

According to scientists, “In systems in which we can observe transitions repeatedly, such as lakes, ranges or fields, and such as human physiology, we may discover where the thresholds are.”

“If we have reason to suspect the possibility of a critical transition, early-warning signals may be a significant step forward in judging whether the probability of an event is increasing,” they added. (ANI)

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Antarctica’s plumbing system more dynamic than previously believed

September 2, 2009 By admin Leave a Comment

Washington, Sept 2 (ANI): Scientists, using space-based lasers on a NASA satellite have created the most comprehensive inventory of lakes that actively drain or fill under Antarctica’s ice, which has revealed a continental plumbing system that is more dynamic than previously thought.

“Even though Antarctica’s ice sheet looks static, the more we watch it, the more we see there is activity going on there all the time,” said Benjamin Smith of the University of Washington in Seattle, who led the study.

Unlike most lakes, Antarctic lakes are under pressure from the ice above. That pressure can push melt water from place to place like water in a squeezed balloon.

The water moves under the ice in a broad, thin layer, but also through a linked cavity system. This flow can resupply other lakes near and far.

Understanding this plumbing is important, as it can lubricate glacier flow and send the ice speeding toward the ocean, where it can melt and contribute to sea level change.

But figuring out what’s happening beneath miles of ice is a challenge.

Researchers led by Smith analyzed 4.5 years of ice elevation data from NASA’s Ice, Cloud and land Elevation satellite (ICESat) to create the most complete inventory to date of changes in the Antarctic plumbing system.

The team has mapped the location of 124 active lakes, estimated how fast they drain or fill, and described the implications for lake and ice-sheet dynamics.

Smith, Helen Fricker, a geophysicist at the Scripps Institution of Oceanography, and colleagues extended their elevation analysis to cover most of the Antarctic continent and 4.5 years of data from ICESat’s Geoscience Laser Altimeter System (GLAS).

By observing how ice sheet elevation changed between the two or three times the satellite flew over a section every year, researchers could determine which lakes were active.

They also used the elevation changes and the properties of water and ice to estimate the volume change.

Only a few of the more than 200 previously identified lakes were confirmed active, implying that lakes in East Antarctica’s high-density “Lakes District” are mostly inactive and do not contribute much to ice sheet changes.

Most of the 124 newly observed active lakes turned up in coastal areas, at the head of large drainage systems, which have the largest potential to contribute to sea level change.

According to Robert Bindschadler, a glaciologist at NASA’s Goddard Space Flight Center, “The survey shows that most active subglacial lakes are located where the ice is moving fast, which implies a relationship.” (ANI)

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Sources of Earth’s “hum” pinpointed

August 9, 2009 By admin Leave a Comment

Washington, August 9 (ANI): A new research has found that the Pacific coasts of North America and Central America are important sources of the Earth’s low-frequency vibration, or “hum”.

Previous studies had found that this hum is excited by infragravity waves, a type of ocean wave that originates in shallow water along coasts, but it was uncertain whether hum is generated primarily by infragravity waves in the deep ocean or along coastlines.

To pinpoint the sources of Earth’s hum, Peter D. Bromirski and Peter Gerstoft from the Scripps Institution of Oceanography, University of California, US, correlated hum intensity data from the EarthScope US Array transportable array with ocean wave height measurements and model simulations.

Their results show that the hum is generated primarily along coasts, with no significant hum generation in the deep ocean.

In particular, they found that the Pacific coasts of North America and Central America are important sources of the hum, and the west coast of Europe is a strong secondary source region, while no significant hum was detected from the Southern Hemisphere during the study period, which is November 2006 to June 2007.

The study is the first to identify these specific source regions for Earth’s hum. (ANI)

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Panama may hold cures to cancer, malaria and dengue fever

July 11, 2009 By admin Leave a Comment

Washington, July 11 (ANI): A team of scientists is exploring the length and breadth of Panama in search of exotic molecules that could one day lead to new treatments for human diseases like cancer, malaria and dengue fever.

The team is being led by William Gerwick from the Scripps Institution of Oceanography at UC (University of California) San Diego.

It was at the island of Coiba off Panama’s Pacific coast, where in June 2004, Kerry McPhail, then a postdoctoral scientist working with Gerwick, discovered a cyanobacterium in shallow water, a primitive photosynthetic organism with features unlike any previously encountered by scientists.

Laboratory analysis and testing revealed that the organism naturally produces a potent cancer-fighting compound.

“To the full extent that we can tell, the compound is working by a novel mechanism to kill cancer cells,” said Gerwick, a scientist with the Scripps Center for Marine Biotechnology and Biomedicine and the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences.

“It has a very unusual molecular structure unlike any we’ve seen before,” he added.

Panama’s location as a bridge between North and South America and a natural thoroughfare for a diverse assortment of migratory land and water species gives it a unique appeal to scientists.

“Despite the fact that we all know Panama because of its famous canal, I have been struck by how remote and primitive and relatively unspoiled large stretches of Panama remain today,” said Gerwick.

Lena Gerwick, a biologist and fellow Scripps researcher, believes that in addition to cancer, the Panamanian environment could be holding biomedically promising sources for treating malaria and tropical diseases such as Chagas’ disease, leishmaniasis, and dengue fever.

Such diseases have been labeled as “neglected” afflictions because they impact millions of people, but have been largely forgotten by the developed world and pharmaceutical companies due to the anticipation of poor returns, and thus few resources are made available to find new treatments for these diseases.

“If you have a lot of diverse organisms, as you find in the tropics, they produce a large diversity of natural products,” said Lena Gerwick.

“There is high competition for every species to carve out its own niche and survive. With that you find a lot of compounds used in defense and other diverse activities. Within this biodiversity might be the next cure for malaria or the next cure for tuberculosis, so there is a great need to conserve it,” she added. (ANI)

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Key culprits in lupus disease identified

June 30, 2009 By admin Leave a Comment

Washington, June 30 (ANI): Scripps Research Institute researchers have identified three new proteins that play a role in the development of lupus erythematosus (or lupus), a chronic inflammatory disease that can affect different body parts, including joints, skin, kidneys, blood cells, heart, and lungs.

Lupus is one of several autoimmune diseases in which the immune system turns against parts of the body, destroying the very cells and tissues it is meant to protect.

Scripps Research Professor of Immunology and Microbial Science Dwight Kono demonstrated that three proteins, called Toll-like receptors (TLRs), are necessary for this autodestruction to occur.

TLRs are proteins found in immune cells that normally help stimulate the initial response of the immune system to foreign pathogens. Humans have 10 different types of TLRs.

While, some of them sit on the surface of immune cells, other TLRs-TLR 3, TLR7, and TLR 9-reside inside immune cells, in a compartment known as the endolysosome, where bits of foreign substances usually end up.

By engineering mice that lack either TLR 7 or TLR9, scientists have gathered evidence that these TLRs may play a role in the disease.

“Earlier studies had strongly suggested that endolysosomal TLRs were important, but if you eliminate one or the other you do not get a huge effect,” said Kono.

To answer this question, Kono and colleagues took advantage of strains of laboratory mice prone to lupus. These mice spontaneously develop many of the same signs and symptoms as humans with the disease.

The next step was to eliminate TLR 3, TLR 7, and TLR 9 in these lupus-prone mice.

They found that the mice lacking functioning TLR 3, TLR 7, and TLR 9 did not develop lupus.

“It seems like these three TLRs are absolutely required for optimal autoantibody production,” said Kono.

“This is an important finding that builds on results obtained by other groups,” Kono added.

The study is published in the Early Edition of the Proceedings of the National Academy of Sciences (PNAS). (ANI)

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Indian-origin girls bag first, third spots in Scripps National Spelling Bee

May 29, 2009 By admin Leave a Comment

Washington, May 29 (ANI): Kansas-based, Indian-origin girl Kavya Shivashankar, 13, has become America’s spelling champion by winning the Scripps National Spelling Bee.

The budding neurosurgeon from Olathe took home more than 40,000 dollars in cash and prizes and the huge champion’s trophy.

The word spelling which she became the victor on Thursday night was “Laodicean”, which means lukewarm or indifferent in religion or politics.

It was Kavya’s fourth appearance at the bee, after having finished 10th, eighth and fourth over the last three years.

Finishing third at this year’s event was another Indian-origin girl from Illinois named Aishwarya Pastapur, 13, reports Fox News.

Second place went to 12-year-old Tim Ruiter of Centreville, Va., the only non-teenager in the finals. He misspelled “maecenas,” which means a cultural benefactor. (ANI)

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Indian scientist says clean cooking stoves can save the planet

April 19, 2009 By admin Leave a Comment

London, Apr 19 (ANI): Soot from mud cooking stoves in tens of thousands of villages in India is emerging as a major source of global warming, according to a leading climate scientist Veerabhadran Ramanathan.

Soot, also known as black carbon, is the second most hazardous gas, after carbon dioxide and is responsible for 18pct of the planet’s warming.

“It’s hard to believe that this is what’s melting the glaciers,” the Scotsman quoted Ramanathan as saying.

Ramanathan suggests that replacing primitive cooking stoves with modern versions that emit far less soot could provide a much-needed solution.

“It is clear to any person who cares about climate change that this will have a huge impact on the global environment,” said Ramanathan, a professor of climate science at the US Scripps Institute of Oceanography, who is working on a project to help poor Indian families acquire new stoves.

“In terms of climate change, we’re driving fast toward a cliff, and this could buy us time,” Ramanathan said.

Unlike carbon dioxide, which lingers in the atmosphere for years, soot stays there for a few weeks.

And converting to low-soot stoves would remove the warming effects of black carbon quickly.

Soot from India has been found in the Maldive islands and on the Tibetan Plateau; from the US, it travels to the Arctic.

In Kohlua, in central India, where there are no cars and little electricity, emissions of carbon dioxide, the main heat-trapping gas linked to global warming, are near zero, and in numerous Indian villages like this one, the environmental and geopolitical implications of soot emissions are enormous.

Ramanathan warned that Himalayan glaciers are expected to lose 75pct of their ice by 2020. (ANI)

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First technique to produce effective anti-leukaemia agent developed

April 18, 2009 By admin Leave a Comment

Washington, Apr 18 (ANI): More than a decade after discovering kapakahines- marine-derived natural products with anti-leukaemia potential-scientists have found the first technique to synthesise them in laboratory in large quantities, by using only acetylene gas, a handful of amino acids, and a dozen inventive steps.

Kapakahines were isolated from a South Pacific sponge in trace quantities, but its lack of availability stalled any future studies.

But, thanks to the efforts of researchers at Scripps Research Institute that unlimited production of kapakahine is now possible.

Thus, research on the compound can proceed and may eventually lead to new drug treatments.

Cripbrochalina olemda, a common tube-type sponge like organism, produces a compound called kapakahine B, among other molecules of interest, which has shown potential for fighting leukaemia.

The researchers have said that kapakahine B, which has an unusual structure, uses some never-before-seen mechanism to fight cancer cells.

For a long time, researchers around the world have unsuccessfully tried to devise a method for synthesizing the kapakahines.

Scripps researchers, led by Phil Baran, started on with more basic research, in which they successfully synthesized a simpler related compound, psychotrimine, with no known pharmaceutical potential.

Inspired by this, the researchers created a highly reactive and selective chemical component referred to as a quaternary centre that, because of structural similarities, also drives the essential first step in the kapakahines synthesis.

Later, they set out on a somewhat riskier venture to develop a second stage needed to synthesize kapakahines.

Then, the researchers predicted that using the quaternary centre, they could produce two intermediate isomers, or molecules with the same chemical formula but different structures.

One of the isomers was predicted to be an ideal stepping stone toward the kapakahines, but more difficult to make.

They predicted that the second isomer would be much more reactive, and in theory its concentration would grow sufficiently as it moved toward equilibrium with the first isomer.

And finally, they synthesized two kapakahines for the first time and in gram quantities.

One of the compounds, kapakahine B, has shown potential in fighting leukaemia cells, which could further help in developing potential drug treatment.

The research has been published online by the Journal of the American Chemical Society. (ANI)

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Scientists solve origin of ocean’s mysterious ‘green glow’

April 2, 2009 By admin Leave a Comment

Washington, April 2 (ANI): Researchers at Scripps Institution of Oceanography at UC (University of California) San Diego have uncovered key clues about bioluminescent worms in the sea that produce a green glow and the biological mechanisms behind their light production.

Research conducted by Scripps marine biologists Dimitri Deheyn and Michael Latz reveals that marine fireworms use bioluminescence to attract suitors in an undersea mating ritual.

The report provides insights into the function of fireworm bioluminescence and moves scientists closer to identifying the molecular basis of the light.

“This is another step toward understanding the biology of the bioluminescence in fireworms, and it also brings us closer to isolating the protein that produces the light,” said Deheyn.

“If we understand how it is possible to keep light so stable for such a long time, it would provide opportunities to use that protein or reaction in biomedical, bioengineering and other fields-the same way other proteins have been used,” he added.

The fireworms used in the study (Odontosyllis phosphorea) are seafloor-dwelling animals that inhabit tropical and sub-tropical shallow coastal areas.

During summer reproductive events known as “swarming,” females secrete a luminous green mucus-which often draws the attention of human seafarers-before releasing gametes into the water.

The bright glow attracts male fireworms, which also release gametes into the bright green cloud.
The precisely timed bioluminescent displays have been tracked like clockwork in Southern California, the Caribbean and Japan, peaking one to two days before each quarter moon phase, 30 to 40 minutes after sunset and lasting approximately 20 to 30 minutes.

Deheyn and Latz collected hundreds of specimens from San Diego’s Mission Bay for their study, allowing them to not only examine live organisms but also produce the fireworms’ luminous mucus for the first time in an experimental setting.

The achievement provided a unique perspective and framework for examining the biology behind the worm’s bioluminescent system.

A central finding is that the fireworms’ bioluminescent light appears to play a role beyond attracting mates.

The researchers found that juveniles produce bioluminescence as flashes, leading to a determination that the light also may serve as a defensive mechanism, intended to distract predators.

Through experiments that included hot and cold testing and oxygen depletion studies, Deheyn and Latz found that the bioluminescence is active in temperatures as low as minus 20 degrees Celsius.

Based on these tests, the researchers believe the chemical process responsible for the bioluminescence may involve a specific light-producing protein-also called a “photoprotein.”

Further identification and isolation will be pursued in future studies. (ANI)

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Termite killer looms as potent greenhouse gas

March 11, 2009 By admin Leave a Comment

Washington, March 11 (ANI): A new study has indicated that fumigant pumped into tented houses to kill pests remains in atmosphere six to 10 times longer than previously thought, thus becoming a potent greenhouse gas.

The study was conducted by a research team led by Jens Muhle, an atmospheric chemist at Scripps Institution of Oceanography, UC (University of California) San Diego.

The team discovered that Sulfuryl fluoride (SO2F2), a gas commonly used to rid buildings of termites and other pests, is a greenhouse gas that remains in the atmosphere about 36 years, six to 10 times longer than previously thought.

The team found that the concentration of the gas rose at a rate of 4 to 6 percent per year between 1978 and 2007, to a global atmospheric abundance by the end of 2007 of about 1.5 parts per trillion.

Its actual emissions into the atmosphere over this period were about one third less than estimated from industrial production data.

“It’s extremely important to have independent verification of emissions,” said Muhle. “You can’t have regulation without verification, and you can’t have verification without measurements,” he added.

Muhle said that he started detecting an unknown compound in air samples taken in early 2004 at the Scripps pier with a newly developed measurement instrument.

He identified the compound as SO2F2 and concluded that the large fluctuations seen at the pier were likely related to the fumigation of local buildings.

The team expanded the analysis to air samples routinely collected around the world at stations of the NASA-funded Advanced Global Atmospheric Gases Experiment (AGAGE) network and to old air samples archived in metal cylinders.

With the help of atmospheric computer models, the Scripps team and colleagues at the Massachusetts Institute of Technology (MIT) determined that the most important removal process of sulfuryl fluoride is dissolution into the ocean, where it is decomposed by chemical reactions.

NOAA researchers working with the Scripps team calculated that one kilogram of SO2F2 emitted into the atmosphere has a global warming potential approximately 4,800 times greater than one kilogram of carbon dioxide.

“Such fumigants are very important for controlling pests in the agricultural and building sectors,” said Ron Prinn, director of MIT’s Center for Global Change Science. “But with methyl bromide being phased out, industry had to find alternatives, so sulfuryl fluoride has evolved to fill the role,” he added.

“Unfortunately, it turns out that sulfuryl fluoride is a greenhouse gas with a longer lifetime than previously assumed,” said Muhle. “This has to be taken into account before large amounts are emitted into the atmosphere,” he added. (ANI)

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New type of vaccination may provide instant immunity against diseases

March 4, 2009 By admin Leave a Comment

Washington, March 3 (ANI): Scripps research scientists say that a new vaccination method they have developed may be used to provide instantaneous protection against diseases caused by viruses and bacteria, cancers, and even virulent toxins.

Professor Carlos Barbas, III, says that tests on mice suggest that the vaccination method called covalent immunization can overcome a major drawback of vaccinations – the lag time of days, or even weeks, that it normally takes for immunity to build against a pathogen.

He revealed that his team tested the vaccination method on mice with either melanoma or colon cancer.

Describing the study in the Proceedings of the National Academy of Sciences (PNAS), the researcher said that the mice were injected with chemicals specifically designed to trigger a programmable and “universal” immune reaction.

They developed other chemicals, “adapter” molecules,” that recognized the specific cancer cells.

The researchers said that after being injected into the mice, the adapter molecules self-assembled with the antibodies to create covalent antibody-adapter complexes.

“The antibodies in our vaccine are designed to circulate inertly until they receive instructions from tailor-made small molecules to become active against a specific target,” Barbas says.

“The advantage of this method is that it opens up the possibility of having antibodies primed and ready to go in the time it takes to receive an injection or swallow a pill. This would apply whether the target is a cancer cell, flu virus, or a toxin like anthrax that soldiers or even civilian populations might have to face during a bioterrorism attack,” adds the researcher.

Barbas revealed that only those mice that had received both the vaccine and the adapter compound generated an immediate immune attack on the cancer cells, which led to significant inhibition of tumour growth.

This is the first time that any research team have successfully designed and tested such a covalent vaccine.

“Our approach differs from the traditional vaccine approach in the sense that when we design an antibody-adapter compound we know exactly what that compound will react with,” Barbas says.

“The importance of this is best exemplified with HIV. In current vaccines, many antibodies are generated against HIV, but most are not able to target the active part of the virus,” the researcher adds.

He is currently planning future studies so that his team may apply their covalent vaccination approach to HIV, cancer, and infectious diseases for which no vaccines currently exist.

“We believe that chemistry-based vaccine approaches have been underexplored and may provide opportunities to make inroads into intractable areas of vaccinology,” Barbas says. (ANI)

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Scientists capture complex movements of enzymes targeted for anti-obesity, anti-cancer drugs

February 13, 2009 By admin Leave a Comment

London, February 12 (ANI): A study led by researchers from Children’s Hospital Oakland Research Institute and The Scripps Research Institute in California has for the first time revealed in great detail how enzymes in the cell cooperate to make fat.

These enzymes are integrated into a single molecular complex known as fatty acid synthase, which is regarded as a potential target for developing new anti-obesity and anti-cancer drugs.

“Fatty Acid Synthase is a remarkably complex structure. It contains all of the components needed to convert carbohydrates into fat,” said Dr. Stuart Smith, of Children’s Hospital Oakland Research Institute.

“We have suspected for some time that the enzyme complex is extremely flexible, which makes it difficult to analyze using X-ray crystallography. Last year the X-ray structure of the complex was solved by a group in Switzerland, but this structure provided only a snapshot of the complex in one of its many poses. We were able to use state-of-the-art electron microscopy to obtain images of the complex in many of its different conformations and assemble these images into a movie that displays the full range of motion of the components of the complex,” the researcher added.

Many drug makers are focusing on inhibitors of fatty acid synthase because they are known to block the conversion of carbohydrates into fat and suppress appetite as well as slow the growth of cancer cells.

The researchers are of the opinion that structural information garnered from X-ray and electron microscope images may aid in the design of more effective inhibitors that could be used therapeutically.

A research article on the study has been published in the journal Nature Structural and Molecular Biology. (ANI)

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Cause of cartilage degeneration in osteoarthritis uncovered

January 14, 2009 By Rajesh Leave a Comment

Washington, Jan 13 (ANI): Scripps research scientists have made a breakthrough discovery by finding the underlying cause of progressive deterioration of the cartilage, which characterises osteoarthritis- loss of the protein HMGB2.

The researchers showed how the loss of HMGB2, found in the surface layer of joint cartilage, leads to degeneration of cartilage in people suffering affected by osteoarthritis.

“We have found the mechanism that begins to explain how and why aging leads to deterioration of articular cartilage. Our findings demonstrate a direct link between the loss of this protein and osteoarthritis,” said Scripps Research Professor Martin Lotz, M.D., a world-renowned arthritis researcher who led the study with Noboru Taniguchi, M.D., Ph.D., a senior research associate in his lab.

Typically, osteoarthritis begins with a disruption of the surface layer of cartilage, called the superficial zone, which triggers an irreversible process that eventually leads to the loss of underlying layers of cartilage until bone begins to grind painfully against bone.

Osteoarthritis most commonly affects the spine, temporomandibular joints, shoulders, hands, hips and knees.

“We knew that the first phase of osteoarthritis is the destruction of cartilage in the superficial zone. Now we know that before this layer is destroyed, there is loss of the critical DNA binding protein HMGB2 and that this loss is directly related to aging,” said Lotz.

It was found that the protein HMGB2 is uniquely expressed on the surface layer of cartilage in joints, where it supports the survival of chondrocytes, the cells that produce and maintain cartilage.

Aging is associated with the loss of HMGB2 and an accompanying reduction or total elimination of chondrocytes in the superficial zone.

In fact, the scientists provided further links between HMGB2 and osteoarthritis by genetically breeding HMGB2 deficient mice that had an earlier and more severe onset of osteoarthritis.

The findings provide a promising avenue to explore the development of new osteoarthritis treatment options.

“If small molecules can be found to prevent or stop the loss of HMGB2, or conversely, to stimulate the production of this protein, then it is possible that osteoarthritis may one day either be prevented or reversed,” said Lotz.

The finding may provide scientists with a clue about how they might be able to engineer the surface layer cartilage.

“As our population ages, osteoarthritis will become an ever-greater health issue. Everyone eventually gets osteoarthritis; even those people who are not functionally impaired by the disease are found to have cartilage damage. And it all starts with the loss of cells in the superficial layer. We now have a starting point for potential prevention, diagnosis, and treatment,” said Lotz.

The scientists describe their work in this week’s Early Edition of the Proceedings of the National Academy of Sciences. (ANI)

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