Spices protect against the consequences of high blood sugar

Herbs and spices are rich in antioxidants, and a new University of Georgia study suggests they are also potent inhibitors of tissue damage and inflammation caused by high levels of blood sugar.

Researchers, whose results appear in the current issue of the Journal of Medicinal Food, tested extracts from 24 common herbs and spices. In addition to finding high levels of antioxidant-rich compounds known as phenols, they revealed a direct correlation between phenol content and the ability of the extracts to block the formation of compounds that contribute to damage caused by diabetes and aging.

“Because herbs and spices have a very low calorie content and are relatively inexpensive, they’re a great way to get a lot of antioxidant and anti-inflammatory power into your diet,” said study co-author James Hargrove, associate professor of foods and nutrition in the UGA College of Family and Consumer Sciences.

Hargrove explained that when blood sugar levels are high, a process known as protein glycation occurs in which the sugar bonds with proteins to eventually form what are known as advanced glycation end products, also known as AGE compounds. The acronym is fitting because these compounds activate the immune system, resulting in the inflammation and tissue damage associated with aging and diabetes.

The researchers found a strong and direct correlation between the phenol content of common herbs and spices and their ability to inhibit the formation of AGE compounds. Spices such as cloves and cinnamon had phenol levels that were 30 percent and 18 percent of dry weight, respectively, while herbs such as oregano and sage were eight and six percent phenol by dry weight, respectively. For comparison, blueberries – which are widely touted for their antioxidant capabilities – contain roughly five percent phenol by dry weight.

Study co-author Diane Hartle, associate professor in the UGA College of Pharmacy, said various phenols are absorbed differently by the body and have different mechanisms of action, so it’s likely that a variety of spices will provide maximum benefit.

“If you set up a good herb and spice cabinet and season your food liberally, you could double or even triple the medicinal value of your meal without increasing the caloric content,” she said.

She added that controlling blood sugar and the formation of AGE compounds can also decrease the risk of cardiovascular damage associated with diabetes and aging. She explained that high blood sugar accelerates heart disease partly because AGE compounds form in the blood and in the walls of blood vessels. The AGE compounds aggravate atherosclerosis, which produces cholesterol plaques.

The UGA researchers tested for the ability to block AGE compounds in a test tube, but animal studies conducted on the health benefits of spices lend support to their argument. Cinnamon and cinnamon extracts, for example, have been shown to lower blood sugar in mice. Interestingly, cinnamon lowers blood sugar by acting on several different levels, Hargrove said. It slows the emptying of the stomach to reduce sharp rises in blood sugar following meals and improves the effectiveness, or sensitivity, of insulin. It also enhances antioxidant defenses.

Hargrove said their findings suggest it’s likely that the herbs and spices they studied will provide similar benefits in animal tests. He points out that because humans have been consuming herbs and spices for thousands of years, they come without the risk of possible side effects that accompany medications.

“Culinary herbs and spices are all generally recognized as safe and have been time-tested in the diet,” he said. “Indeed, some of spices and herbals are now sold as food supplements because of their recognized health benefits.”

Study co-author Phillip Greenspan, associate professor in the College of Pharmacy, noted that most people don’t get their recommended five to nine servings of fruits and vegetables a day. Rather than seasoning their food with salt – which provides no beneficial phenols and has been linked to high blood pressure – he recommends that people use a variety of herbs and spices to help boost the nutritional quality of their meals.

“When you add herbs and spices to food, you definitely provide yourself with additional benefits besides taste,” Greenspan said.

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Article adapted by MD Only from original press release.
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Contact: Sam Fahmy
University of Georgia

Stress at Work Interfers with Sleep

Common hassles at work are more likely than long hours, night shifts or job insecurity to follow workers home and interfere with their sleep. That’s the conclusion of a University of Michigan study presented April 17 at the annual meeting of the Population Association of America. The study analyzes two nationally representative surveys of approximately 2,300 U.S. adults that monitored the same workers for up to a decade. Over that time, roughly half the respondents said they had trouble sleeping. “Together, work and sleep take up about two-thirds of every weekday,” said U-M sociologist Sarah Burgard. “But until now, very little research has focused on the connections between work and sleep for the average U.S. worker.”

Previous research has shown that lack of sleep can have serious consequences ranging from traffic accidents to health problems, chronic disease and mortality. As many as 70 million Americans suffer from some kind of chronic sleep disorder. But this is the first U.S. study to clarify the link between work and sleep quality for all workers, not just rotating shift workers or medical students, who have unusual work and sleep arrangements.

Because the surveys were prospective—following the same people over time—the researchers were able to show that work conditions affected sleep patterns, not the other way around. Their analysis controlled for initial sleep quality, health, pessimism and other confounding factors. Respondents who felt upset or bothered at work on a frequent basis, or had on-going personal conflicts with bosses or co-workers, were about 1.7 times more likely than others to develop sleep problems. “Massive changes over the past half-century have reshaped the workplace, with major implications for sleep,” Burgard said. “For many workers, psychological stress has replaced physical hazards. “Physical strain at work tends to create physical fatigue and leads to restorative sleep, but psychological strain has the opposite effect, making it more difficult for people to sleep.”

Burgard and graduate student Jennifer Ailshire also explored how work-family conflict, gender, education and job status affected the relationship between work and sleep. As women have entered the labor force in large numbers, dual-earner households and single-parent families have made the time-crunch a major factor, Burgard said. As expected, Burgard and Ailshire found that work-family conflicts and the presence of children under the age of three were significant predictors of negative changes in sleep quality.

Respondents with children under the age of three were about 2.2 times as likely to report poor sleep quality, but having young children did not explain the association between hassles at work and sleep quality. Surprisingly, however, they found no evidence that long hours, or working nights or weekends—strategies often adopted by working parents to juggle childcare and jobs while minimizing the use of baby-sitters or daycare facilities—had a negative impact on reported sleep quality.

In future research, Burgard plans to explore factors that could buffer workers from negative working conditions, such as age and a sense that one’s job is useful or helpful to others. She also plans to examine interventions that could break the link between work conditions and troubled sleep.

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Article adapted by MD Only from original press release.
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Sarah Burgard Ph.D., M.S. Burgard is assistant professor of sociology at the U-M College of Literature, Science, and the Arts; assistant professor of epidemiology at the U-M School of Public Health; and assistant research scientist at the U-M Institute for Social Research (ISR).

Source: Diane Swanbrow
University of Michigan

A brisk walk daily is the easiest way to trim waistline

Research from Duke University Medical Center shows that even a modest amount of brisk walking weekly is enough to trim waistlines and cut the risk of metabolic syndrome (MetS), an increasingly frequent condition linked to obesity and a sedentary lifestyle.

It’s estimated that about a quarter of all U.S. adults have MetS, a cluster of risk factors associated with greater likelihood of developing heart disease, diabetes and stroke: large waist circumference, high blood pressure, high levels of triglycerides, low amounts of HDL, or “good” cholesterol, and high blood sugar. To be diagnosed with MetS, patients must have at least three of these five risk factors, and according to many studies, a growing number of people do.

But Johanna Johnson, a clinical researcher at Duke Medical Center and the lead author of a new study examining the impact of exercise on MetS, said a person can lower risk of MetS by walking just 30 minutes a day, six days per week. “That’s about 11 miles per week. And our study shows that you’ll benefit even if you don’t make any dietary changes.”

“The results of our study underscore what we have known for a long time,” said Duke cardiologist William Kraus. “Some exercise is better than none; more exercise is generally better than less, and no exercise can be disastrous.”

The study appears in the December 15 issue of the American Journal of Cardiology.

The results come from a multi-year, federally funded study called STRRIDE (Studies of a Targeted Risk Reduction Intervention through Defined Exercise) that examined the effects of varying amounts and intensity of exercise on 171 middle-aged, overweight men and women.

Before exercising regularly, 41 percent of the participants met the criteria for MetS. At the end of the 8-month exercise program, only 27 percent did.

“That’s a significant decline in prevalence,” said Johnson. “It’s also encouraging news for sedentary, middle-aged adults who want to improve their health. It means they don’t have to go out running four or five days a week; they can get significant health benefits by simply walking around the neighborhood after dinner every night.”

Still, some exercise regimens were better than others. Those who exercised the least, walking about 11 miles per week, gained significant benefit, while those who exercised the most, jogging about 17 miles per week, gained slightly more benefit in terms of lowered MetS scores.

One group puzzled the researchers, however. Those who did a short period of very vigorous exercise didn’t improve their MetS scores as much as those who performed less intense exercise a longer period.

Kraus said there may be more value in doing moderate intensity exercise every day rather than more intense activity just a few days a week.

In all three of the study’s exercise groups, waistlines got smaller over the 8-month period. In general, men who exercised saw greater improvement in their MetS risk factors than women. But Johnson points out that at baseline, the men generally had worse scores than women, “so they had more room to improve,” she said.

Over the course of the STRRIDE study, the inactive control group – those who didn’t change their diet or activity level at all – gained an average of about one pound and a half-inch around the waist. “That may not sound like much, but that’s just six months,” Kraus said. “Over a decade, that’s an additional 20 pounds and 10 inches at the beltline.”

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Article adapted by MD Only Weblog from original press release.
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Contact: Michelle Gailiun
Duke University Medical Center

The study was funded by the National Institutes of Health.

Colleagues at Duke who contributed to the study include Cris Slentz, Gregory Samsa, Lori Bateman and Brian Duscha. Collaborating authors from East Carolina University include Joseph Houmard, Jennifer McCartney and Charles Tanner.

Plant pigment in cherries helps lower sugar levels

Perhaps George Washington wouldn’t have chopped down his father’s cherry tree if he knew what chemists now know. They have identified a group of naturally occurring chemicals abundant in cherries that could help lower blood sugar levels in people with diabetes. In early laboratory studies using animal pancreatic cells, the chemicals, called anthocyanins, increased insulin production by 50 percent, according to a peer-reviewed study scheduled to appear in the Jan. 5 issue of the American Chemical Society’s Journal of Agricultural and Food Chemistry. ACS is the world’s largest scientific society.Anthocyanins are a class of plant pigments responsible for the color of many fruits, including cherries. They also are potent antioxidants, highly active chemicals that have been increasingly associated with a variety of health benefits, including protection against heart disease and cancer.

“It is possible that consumption of cherries and other fruits containing these compounds [anthocyanins] could have a significant impact on insulin levels in humans,” says study leader Muralee Nair, Ph.D., a natural products chemist at Michigan State University in East Lansing. “We’re excited with the laboratory results so far, but more studies are needed.” Michigan is the top cherry producing state in the nation.

Until human studies are done on cherry anthocyanins, those with diabetes should continue following their doctor’s treatment recommendations, including any medicine prescribed, and monitor their insulin carefully, the researcher says. The compounds show promise for both the prevention of type 2 (non-insulin-dependent) diabetes, the most common type, and for helping control glucose levels in those who already have diabetes, he adds.

While fresh cherries and fruits containing these anthocyanins are readily available, medicinal products may be the most efficient way to provide the beneficial compounds, according to Nair. It’s possible that anthocyanins eventually could be incorporated into new products, such as pills or specialty juices that people could take to help treat diabetes. Such disease-specific products may take several more years to develop, he notes.

Scientists in Nair’s laboratory have even developed a unique process, patented by the university, for removing sugar from fruit extracts that contain anthocyanins. This could lead to “sugar-free” medicinal products for people with diabetes.

The current study, partially funded by the U.S. Department of Agriculture, involved tart cherries (also known as sour cherries or pie cherries), a popular variety in the United States, and the Cornelian cherry, which is widely consumed in Europe. Nair and his associates, B. Jayaprakasam, Ph.D., L.K. Olson, Ph.D., and graduate student S. K. Vareed, tested several types of anthocyanins extracted from these cherries against mouse pancreatic-beta cells, which normally produce insulin, in the presence of high concentrations of glucose.

Insulin is the protein produced by the pancreas that helps regulate blood sugar (glucose) levels. Compared to cells that were not exposed to anthocyanins, exposed cells were associated with a 50 percent increase in insulin levels, the researchers say. The mechanism of action by which these anthocyanins boost insulin production is not known, Nair says.

Nair and his colleagues are currently feeding anthocyanins to a group of obese, diabetic mice to determine how the chemicals influence insulin levels in live subjects. Results of these tests are not yet available.

Although other fruits, including red grapes, strawberries and blueberries, also contain anthocyanins, cherries appear to be the most promising source of these compounds on the basis of serving size, according to the researcher. The compounds are found in both sweet and sour (tart) cherry varieties.

The potential benefits of cherries extend beyond diabetes. Previous studies by the researcher found that certain anthocyanins isolated from cherries have anti-inflammatory properties and may be useful in fighting arthritis. Nair’s colleagues have found that cherries also may help fight colon cancer.

But people with diabetes are encouraged to use caution when it comes to consuming maraschino cherries, the bright red candied version that adorns ice cream and cocktails, Nair points out. Many of the beneficial cherry pigments that were present in the fresh fruit have been removed during processing, replaced with food coloring, and extra sugar has been added.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

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Article adapted by MD Only Weblog from original press release.
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Contact: Michael Bernstein
American Chemical Society

Menopause can make you fat

New research on the effects of the female sex hormone estrogen in the brain lend credence to what many women have suspected about the hormonal changes that accompany aging: Menopause can make you fat.Scientists long have sought to understand how changes in hormones during menopause could account for the increase in appetite and accompanying weight gain that often occurs among aging women.

In a series of animal experiments described today at the 234^th national meeting of the American Chemical Society, the world’s largest scientific society, researchers showed how estrogen receptors located in the hypothalamus serve as a master switch to control food intake, energy expenditure and body fat distribution. When these receptors are destroyed, the animals immediately begin to eat more food, burn less energy and pack on pounds.

This research seems to support a link between estrogen and regulation of obesity, especially the dangerous accumulation of abdominal fat linked to heart disease, diabetes, and cancer, says Deborah J. Clegg, Ph. D., assistant professor of psychiatry at the University of Cincinnati Academic Health Center, who is directing the studies.

The findings may also help scientists develop more targeted hormone replacement therapies, capable of stimulating estrogen receptors in one part of the brain or body while dampening it in the next, Clegg says.

Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.

To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.

Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.

When estrogen levels in the VMN dipped, the animals’ metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.

The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.

Clegg now plans to perform a similar experiment to deactivate ER-alpha in the arcuate nucleus region of the hypothalamus. This region contains two populations of neurons: one puts the brake on food intake and the other stimulates food intake. Clegg anticipates that a loss of estrogen in this region may create an increase in the animals’ appetites as well as their weight.

Clegg says her studies address an area that is sorely needed given the incidence and impact of gender differences in obesity and its complications.

“The accumulation of abdominal fat puts both men and women at a heightened risk of cardiovascular disease, diabetes, and insulin resistance,” she says. “Women are protected from these negative consequences as long as they carry their weight in their hips and saddlebags. But when they go through menopause and the body fat shifts to the abdomen, they have to start battling all of these medical complications.”

By identifying the critical brain regions that determine where body fat is distributed, Clegg says her findings may help scientists design hormone replacement therapies to better manage and manipulate estrogen levels.

“If we could target those critical regions and estrogen receptors associated with weight gain and energy expenditure, we could perhaps design therapies that help women sidestep many of the complications brought on by the onset of menopause,” she says.

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Article adapted by MD Only Weblog from original press release.
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Contact: Charmayne Marsh
American Chemical Society

The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

—Deborah J. Clegg, Ph.D., is assistant professor of psychiatry at the University of Cincinnati Academic Health Center in Cincinnati, Ohio.

How Exercise Stops Memory Loss

Research has shown that people who exercise do better on memory tests. Now a new Columbia University Medical Center study explains specifically what exercise does within the brain. Exercise, the researchers found, targets a region of the brain within the hippocampus, known as the dentate gyrus, which underlies normal age-related memory decline that begins around age 30 for most adults.

This finding is significant because it was accomplished via the first-ever observation of neurogenesis, the growth of neurons, within a living brain. Using an MRI imaging technique developed at Columbia, the researchers were able to identify neurogenesis within the dentate gyrus region following exercise. Previously, researchers were only able to prove neurogenesis upon postmortem exam in animal studies.

“No previous research has systematically examined the different regions of the hippocampus and identified which region is most affected by exercise,” said Scott A. Small, M.D., associate professor of neurology at Columbia University Medical Center and the study’s lead author. “I, like many physicians, already encourage my patients to get active and this adds yet another reason to the long list of reasons why exercise is good for overall health.”

Published in the March 12-16, 2007 early online edition of the Proceedings of the National Academy of Sciences, the finding builds upon previous research at Columbia that identified the role of the dentate gyrus region of the hippocampus in normal age-related memory decline. Additionally, Fred “Rusty” Gage, Ph.D. of the Salk Institute, a lead co-investigator on this study, had demonstrated in mice that the dentate gyrus is the one area of the brain where new neurons are generated, and that exercise improves this process. This is the first human study to emerge out of this observation.

“Our next step is to identify the exercise regimen that is most beneficial to improve cognition and reduce normal memory loss, so that physicians may be able to prescribe specific types of exercise to improve memory,” said Dr. Small, who is also a research scholar at the Columbia University Taub Institute for Research on Alzheimer’s Disease and the Aging Brain.

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Article adapted by MD Only Weblog from original press release.
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Contact: Elizabeth Streich, Columbia University Medical Center

Additional Columbia researchers who contributed to this study include: Ana C. Pereira, Rene Hen, Dan E. Huddleston, Adam M. Brickman, Alexander A. Sosunov, Guy M. McKhann, Truman R. Brown and Richard Sloan.

The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center is a multidisciplinary group that has forged links between researchers and clinicians to uncover the causes of Alzheimer’s, Parkinson’s and other age-related brain diseases and discover ways to prevent and cure these diseases. It has partnered with the Gertrude H. Sergievsky Center at Columbia University Medical Center which was established by an endowment in 1977 to focus on diseases of the nervous system. The Center integrates traditional epidemiology with genetic analysis and clinical investigation to explore all phases of diseases of the nervous system.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions.

Magnesium shown to reverse memory loss

Magnesium helps build bones, make proteins, release energy stored in muscles and regulate body temperature. In the cover story of the Dec. 2 issue of Neuron, MIT researchers report a possible new role for magnesium: helping maintain memory function in middle age and beyond.

The adult daily nutritional requirement for magnesium, a trace mineral found in foods such as dark green, leafy vegetables, is around 400 mg a day. But studies show that as many as half of all Americans do not consume enough magnesium. Magnesium deficits have been tied to allergies, asthma, attention deficit disorder, anxiety, heart disease, muscle cramps and other conditions.

Associate Professor Guosong Liu and postdoctoral associate Inna Slutsky at MIT’s Picower Center for Learning and Memory found that magnesium helps regulate a key brain receptor important for learning and memory. Their work provides evidence that a magnesium deficit may lead to decreased memory and learning ability, while an abundance of magnesium may improve cognitive function.

“Our study shows maintaining proper magnesium in the cerebrospinal fluid is essential for maintaining the plasticity of synapses,” the authors wrote. “Since it is estimated that the majority of American adults consume less than the estimated average requirement of magnesium, it is possible that such a deficit may have detrimental effectsSresulting in potential declines in memory function.”

Plasticity, or the ability to change, is key to the brain’s ability to learn and remember. Synapses, the connections among brain cells, undergo physical changes in response to brain activity. While the mechanisms underlying these changes remain elusive, it is known that synapses are less plastic in the aging or diseased brain. Loss of plasticity in the hippocampus, where short-term memories are stored, causes the forgetfulness common in older people.

“The important issue is how the plasticity of synapses is regulated physiologically,” said Liu, who has appointments in MIT’s Department of Biology and Department of Brain and Cognitive Sciences. Working with Slutsky, graduate student Safa Sadeghpour and technician Bing Li, Liu identified a key principle that predicts which chemicals can enhance plasticity.

This finding is akin to the difference between hearing music on an old radio or a high-fidelity stereo. Synapses, like speakers, have a level of background noise that can get in the way of transmitting their signal from one neuron to another. Just as our ears become more sensitive to nuances in music played on a top-of-the-line music system, synapses become more plastic when background noise is reduced.

Armed with this new understanding, the researchers then identified magnesium’s importance in synaptic function.

Magnesium is the gatekeeper for the NMDA receptor, which receives signals from an important excitatory neurotransmitter involved in synaptic plasticity. Magnesium helps the receptor open up for meaningful input and shut down to background noise. “As predicted by our theory, increasing the concentration of magnesium and reducing the background level of noise led to the largest increases of plasticity ever reported in scientific literature,” Liu said.

The researchers have identified and are now studying several families of drugs that may restore learning and memory in animals. Most important, Liu said, “This new theory may help create strategies to prevent aging-induced loss of synaptic plasticity.”

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Article adapted by MD Only Weblog from original press release.
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Contact: Sean Wagner
MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA 02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

This work was supported by the RIKEN-MIT Neuroscience Center and the National Institutes of Health.

A version of this article appeared in MIT Tech Talk (download PDF).

Memory Loss… Cognitive Decline and Dementia Linked to Diet

Research has shown convincing evidence that dietary patterns practiced during adulthood are important contributors to age-related cognitive decline and dementia risk. An article published in Annals of the New York Academy of Sciences highlights information on the benefits of diets high in fruit, vegetables, cereals and fish and low in saturated fats in reducing dementia risk.

Adults with diabetes are especially sensitive to the foods they eat with respect to cognitive function. Specifically, an adult with diabetes will experience a decline in memory function after a meal, especially if simple carbohydrate foods are consumed. While the precise physiological mechanisms underlying these dietary influences are not completely understood, the modulation of brain insulin levels likely contributes.

This deficit can be prevented through healthful food choices at meals. The findings suggest that weight maintenance reduces the risk of developing obesity-associated disorders, such as high blood pressure and high cholesterol, and is an important component of preserving cognitive health.

The work shows another benefit of maintaining healthful eating practices with aging – the same ones proposed by most diabetes and heart & stroke foundations. “This type of information should be able to empower the individual, knowing that he/she can be actively engaged in activities and lifestyles that should support cognitive health with aging,” says Carol Greenwood, author of the study.

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Article adapted by MD Only Weblog from original press release.
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Contact: Sean Wagner
http://www.blackwellpublishing.com

_________________________________________________________________
This study, entitled “Dietary Influences on Cognitive Function with Aging,” is published in volume 1114 of the Annals of the New York Academy of Sciences: Healthy Aging and Longevity.

To view the abstract for this article, please http://www.blackwell-synergy.com/doi/abs/10.1111/j.1468-0009.2007.00496.x http://www.blackwell-synergy.com/doi/abs/10.1111/j.1540-627X.2007.00220.x http://www.blackwell-synergy.com/doi/abs/10.1111/j.1523-536X.2007.00172.x http://www.blackwell-synergy.com/">click here.

Smart Bone Cells May Add or Remove 3% Bone Mass Per Month

Liyun Wang, UD assistant professor of mechanical engineering, views osteocytes (bone cells) in her lab, as graduate students Wen Li and Xiaozhou Zhou examine the magnified images in the background.  Click here for more information.

Ten million people in the United States are estimated to already have bone diseases, and almost 34 million more are estimated to have low bone mass, putting them at increased risk for osteoporosis, according to the National Osteoporosis Foundation.

Liyun Wang, assistant professor of mechanical engineering at the University of Delaware, knows the serious consequences of osteoporosis.

Two of Wang’s aunts have suffered from the insidious bone-thinning disease, and one aunt died within a year after falling and fracturing her hip.

Wang is now leading research that will shed light on how osteocytes–the cells encased inside your bones–sense external stimuli and communicate with cells on the surface, signaling them to either build more bone or remove existing bone.

The five-year, $1.6 million project, ranked in the top 5 percent of research proposals recommended for funding by the National Institutes of Health (NIH) this year, holds promise in unveiling the mysteries of bone and joint diseases afflicting people worldwide.

The results may not only help scientists home in on the cause of osteoporosis and arthritis, but also develop more effective drug therapies to treat the debilitating bone and joint diseases.

The project will involve an interdisciplinary team of investigators at UD, including Prof. Mary C. Farach-Carson and Associate Prof. Randall Duncan, who hold primary appointments in biological sciences with joint appointments in mechanical engineering, and John Novotny, assistant professor of mechanical engineering.

“Bone and joint disorders affect almost half of all people over 50 years old, at a cost of $250 billion annually in the United States,” Wang said. “A third of the people who suffer a fracture due to bone loss end up dying within a year.”

The embedded bone cells, or osteocytes, that Wang is studying, act like the bone’s “brain.”

“The osteocytes are very smart,” Wang says. “They can tell whether a person is using his or her bones or not. If the person is physically active, the osteocytes tell cells on the surface that it’s okay to put on more bone. Otherwise, they signal the surface cells to remove bone at a rate that can be as high as 3 percent bone mass per month, which is the case for patients confined to long-term bed rest and for astronauts,” she notes.

The osteocytes lie in tiny pits or holes, called lacunae, within the bone. These living cells have many long arms that connect them to surface bone cells and the bone’s vascular system. The narrow channels housing the osteocyte’s arms (canaliculi) and the lacunae form a network through which a mixture of water, nutrients and other bioactive molecules flows.

“Although it is hard as cement, bone is actually like a stiff sponge,” Wang says. “It’s porous and has water inside. When we have mechanical loading, when you run, for example, a part of the leg bone is compressed, and water is pushed through gaps, less than a micrometer in size, between the osteocytes and the bone cement that surrounds them.”

This powerful wave of fluid keeps the osteocytes happy and functioning well, Wang says, delivering nutrients to them from nearby blood vessels and quickly dispersing signaling molecules, such as calcium ions, from one cell to its neighbors.

Using a novel microscopic imaging method that Wang developed, which is based on fluorescence recovery after photobleaching (FRAP), the research team hopes to do what no one has done before: see inside living bone and determine how rapidly these signaling and nutrient molecules are transferred between the cells when a bone is at rest and when it is at work.

A high-powered laser-scanning microscope will be used to assess the movement of molecules in the tibia of an anesthetized mouse. A harmless green fluorescent dye, tagged to various-sized proteins, signaling molecules and cell nutrients, will be injected into the animal’s bloodstream.

The dyed molecules will be subjected to a flash of intense light, temporarily photobleaching them black, leaving a distinct black sector surrounded by green. Thus, if the molecules diffuse into one another’s territories, they can easily be tracked by color.

Using similar techniques, Wang is investigating the communication between bone and cartilage in the development and progression of osteoarthritis, one of five projects in an $11 million NIH grant led by Thomas Buchanan, professor and chairperson of the UD Department of Mechanical Engineering. The UD effort includes a unique mentoring program for women scientists.

Wang says she is grateful for the mentoring and support she has received from her colleagues at UD since she joined the faculty in 2005, as well as from her doctoral advisers at the City College of New York, including Profs. Susannah Fritton, Steve Cowin, and Sheldon Weinbaum; and Dr. Mitchell Schaffler, with whom she worked as a postdoctoral researcher at the Mt. Sinai School of Medicine.

Currently, Wang’s laboratory group includes Wen Li, a graduate student in biomechanics and movement science, Xiaozhou Zhou, a graduate student in mechanical engineering, and undergraduate students Ben Keller and Laura Schultz, who are both working on degrees in mechanical engineering, and Samantha Nigro, who is pursuing her degree in biological sciences. Research associate Jun Pan will join the group at the end of this year.

“My students have been excellent,” Wang says, smiling. “They are well-organized and eager to learn how to do research. They are very motivated, and that is important. We have exciting work ahead of us!”

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Article adapted by MD Only Weblog from original press release.
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Contact: Tracey Bryant
tbryant@udel.edu
302-831-8185
University of Delaware

Wang is seeking two additional doctoral students and one postdoctoral researcher in the areas of biomechanics, orthopedic biology or mechanical engineering to join her research team. For more information, contact Wang at [lywang@udel.edu].

Stanford/Packard scientists discovery way to speed bone healing

Blocking a naturally occurring inhibitor of bone formation accelerates healing of skull defects in mice, say researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital. The finding advances the understanding of how the skeleton develops and opens new therapeutic avenues for many of the disorders that are expected to afflict aging baby boomers.

“This could potentially lead to much more effective therapies for how we replace bone or promote bone healing,” said Michael Longaker, MD, professor of plastic and reconstructive surgery. “Let’s say I’m an 80-year-old with a fractured hip. It would be invaluable to be able to heal more quickly and regain mobility and strength.”

The study will be published in the Sept. 7 issue of the Journal of Biological Chemistry.
Scientists have known for some time about a class of proteins called bone morphogenetic proteins, or BMPs, which stimulate bone formation. In fact, some current therapies for stimulating bone formation, such as spinal fusions, use recombinant BMPs to help healing. But Longaker’s new study of a protein called Noggin, which blocks bone growth, suggests there might be another, more efficient approach.

Noggin was first identified in 1992 by one of Longaker’s collaborators, Richard Harland, PhD, now a faculty member at the University of California-Berkeley, as a protein that guides tissue fate in developing frog embryos. In 2003, the researchers found that Noggin prevents the premature fusion of bones in the skull during infancy by blocking the actions of BMPs.

Longaker and the first author of the new study, Derrick Wan, MD, a postdoctoral scholar at Stanford, wondered whether interfering with Noggin expression could speed bone growth.In the new study, they initially found through work with tissue cultures that using small pieces of RNA to block Noggin expression in bone-forming cells increased the activity of the cells’ BMPs and nudged them further down the bone-producing path. Furthermore, bone-forming cells in which Noggin expression was suppressed were able to heal large skull defects in mice significantly more quickly than Noggin-expressing cells.

“Basically we just took away the natural brake and let the accelerator go to town,” said Longaker, who is also a pediatric craniofacial surgeon at Packard Children’s Hospital.

Despite the accelerated rate of healing seen in the mice treated with the Noggin-challenged cells, bone formation didn’t run rampant in these animals. After eight weeks, the healed skulls of the two groups of mice looked similar. This is important because over-enthusiastic bone formation could exacerbate rather than solve musculo-skeletal problems.

“The bone that was formed looked very normal,” said Longaker. “It’s not as if these mice grew horns or anything.”

In addition to the obvious therapeutic implications, the discovery of the interplay between Noggin and BMPs also sheds light on a perplexing developmental mystery: What guides skeletal formation during embryogenesis, when BMPs are expressed in many cells not destined to become bone? Now it appears that Noggin, along with other potent BMP inhibitors, keeps the BMPs in check throughout most of the body. This type of yin-yang relationship keeps the body primed to respond quickly to damage like fractures.

Although the concept needs to be tested in humans, the researchers envision a day when many disorders could benefit by tweaking Noggin levels up or down.

“Think of the way we treat arthritis,” said Longaker. “Right now, we cut off the diseased part of the joint and glue in a metal implant. Imagine if we could instead use a biodegradable replacement seeded with a compound that could knock down Noggin expression in the area and slowly secrete BMPs. Over two or three years, the implant would dissolve, to be replaced by the individual’s own healthy bone. This is a first step toward the concept of personalized bone tissue engineering.”

In addition to Wan, Longaker’s Stanford collaborators include Jason Pomerantz, MD, postdoctoral scholar; Jae-Beom Kim, PhD, research associate; and Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology. Longaker also collaborated with researchers at UCLA.

The research was funded by the National Institutes of Health, the Oak Foundation, a Ruth L. Kirschstein National Research Service Award, and an Ethicon-Society of University Surgeons Research Fellowship.

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Article adapted by MD Only Weblog from original press release.
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Contact: Krista Conger
Stanford University School of Medicine