Finding promise new treatments for tendon injury and disease
Los Angeles, Sept. 7, 2007—Athletes know that damage to a tendon can signal an end to their professional careers. But a consortium of scientists, led in part by University of Southern California (USC) School of Dentistry researcher Songtao Shi, has identified unique cells within the adult tendon that have stem-cell characteristics—including the ability to proliferate and self-renew. The research team was able to isolate these cells and regenerate tendon-like tissue in the animal model. Their findings hold tremendous promise for the treatment of tendon injuries caused by overuse and trauma.
The results of their research will be published in the October 2007 issue of the journal Nature Medicine and will be available online at http://www.nature.com/nm on Sunday, September 9, 2007.
Tendons, the tough band of specialized tissues that connect bone to muscle, are comprised of strong collagen fibrils that transmit force allowing the body to move. Tendon injuries are a common clinical problem as damaged tendon tissue heals slowly and rarely regains the integrity or strength of a normal, undamaged tendon.
“Clinically, tendon injury is a difficult one to treat, not only for athletes but for patients who suffer from tendinopathy such as tendon rupture or ectopic ossification,” Shi says. “This research demonstrates that we can use stem cells to repair tendons. We now know how to collect them from tissue and how to control their formation into tendon cells.”
Prior to this research, little existed on the cellular makeup of tendons and their precursors. By looking at tendons at the molecular level, the research team identified a unique cell population—termed tendon stem/progenitor cells (TSPCs) in both mice and adult humans—that when guided by a certain molecular environment, form into tendon cells. The team included leading scientists from the National Institute of Dental and Craniofacial Research at the National Institutes of Health, Johns Hopkins University and the University of Maryland School of Medicine.
Songtao Shi, a researcher for USC’s Center for Craniofacial Molecular Biology, a Division within the USC School of Dentistry, has published numerous studies on the role of stem cells in regeneration. He was part of an international research team that successfully generated tooth root and supporting periodontal ligaments to restore tooth function in the animal model. Earlier this year, his research was published in the journal Stem Cells after he and his team discovered that mesenchymal stem cells are capable of regenerating facial bone and skin tissue in the mouse and swine models.
Funding for the study came from the USC School of Dentistry and the National Institutes of Health.
Yanming Bi, Driss Ehirchiou, Tina M Kilts, Colette A Inkson, Mildred C Embree, Wataru Sonoyama, Li Li, Arabella I Leet, Byoung-Moo Seo, Li Zhang, Songtao Shi & Marian F Young. “Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.” Nature Medicine, http://www.nature.com/nm
USC’s Center for Craniofacial Molecular Biology
USC’s Center for Craniofacial Molecular Biology is a research laboratory located on the Health Sciences Campus of the University of Southern California in Los Angeles. Administratively, CCMB is part of the USC School of Dentistry. The laboratory is funded through multiple research grants, including several from the National Institutes of Health, under which research is conducted into development, biochemical and molecular biological aspects of human development, with a special emphasis on craniofacial structures in both health and disease. Current investigations include the molecular etiology of cleft palate, the molecular genetics of tooth development and lung development in the premature infant.
Contact: Angelica Urquijo
University of Southern California
-It helps to prevent diseases such as anaemia and bone demineralisation
-UGR researchers have carried out a comparative study on the properties of goat milk compared to those of cow milk. Rats with induced nutritional ferropenic anaemia have been used in the study
-Goat milk helps digestive and metabolic utilisation of minerals such as iron, calcium, phosphorus and magnesium
-Part of the results of this research have been published in the prestigious scientific journals International Dairy Journal and Journal Dairy Science
C@MPUS DIGITAL Research carried out at the Department of Physiology of the University of Granada has revealed that goat milk has more beneficial properties to health than cow milk. Among these properties it helps to prevent ferropenic anaemia (iron deficiency) and bone demineralisation (softening of the bones).
This project, conducted by Doctor Javier Díaz Castro and directed by professors Margarita Sánchez Campos, Mª Inmaculada López Aliaga and Mª José Muñoz Alférez, focuses on the comparison between the nutritional properties of goat milk and cow milk, both with normal calcium content and calcium enriched, against the bioavailability of iron, calcium, phosphorus and magnesium. To carry out this study, the metabolic balance technique has been used both in rats with experimentally induced nutritional ferropenic anaemia and in a control group of rats.
In order to know how the nutritive utilisation of these minerals may affect their metabolic distribution and destination, the UGR researcher has determined the concentration of these minerals in the different organs involved in their homeostatic regulation and different haematological parameters in relation to the metabolism of the minerals.
Better results with goat milk
Results obtained in the study reveal that ferropenic anaemia and bone demineralisation caused by this pathology have a better recovery with goat milk. Due to the higher bioavailability of iron, calcium, phosphorus and magnesium, the restoration of altered haematological parameters and the better levels of parathyroid hormone (PTH), a hormone that regulates the calcium balance in the organism was found in the rats that consumed this food.
Javier Díaz Castro points out that the inclusion of goat milk with normal or double calcium content in the diet “favours digestive and metabolic utilisation of iron, calcium and phosphorus and their deposit in target organs – parts of the organism to which these minerals are preferably sent – involved in their homeostatic regulation”.
According to this researcher, all these conclusions reveal that regular consumption of goat milk – a natural food with highly beneficial nutritional characteristics – “has positive effects on mineral metabolism, recovery from ferropenic anaemia and bone mineralisation in rats. In addition, and unlike observations in cow milk, its calcium enrichment does not interfere in the bioavailability of the minerals studied”.
Although there is no doubt that these findings may be a base for further in depth study of the multiple health benefits of goat milk, the UGR researcher warns that “studies in humans are still required in order to confirm the findings obtained in rats and to promote goat milk consumption both in the general population and in the population affected by nutritional ferropenic anaemia and pathologies related to bone demineralisation”. Part of the results of this research has been published in the prestigious scientific journals International Dairy Journal and Journal Dairy Science.
Reference: Dr Javier Díaz Castro. Department of Physiology of the University of Granada.
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Scientists have only recently begun to speculate that what’s referred to as “junk” DNA – the 96 percent of the human genome that doesn’t encode for proteins and previously seemed to have no useful purpose – is present in the genome for an important reason. But it wasn’t clear what the reason was. Now, researchers at the University of California, San Diego (UCSD) School of Medicine have discovered one important function of so-called junk DNA.
Genes, which make up about four percent of the genome, encode for proteins, “the building blocks of life.” An international collaboration of scientists led by Michael G. Rosenfeld, M.D., Howard Hughes Medical Investigator and UCSD professor of medicine, found that some of the remaining 96 percent of genomic material might be important in the formation of boundaries that help properly organize these building blocks. Their work will be published in the July 13 issue of the journal Science.
“Some of the ‘junk’ DNA might be considered ‘punctuation marks’ – commas and periods that help make sense of the coding portion of the genome,” said first author Victoria Lunyak, Ph.D., assistant research scientist at UCSD.
In mice, as in humans, only about 4 percent of the genome encodes for protein function; the remainder, or “junk” DNA, represents repetitive and non-coding sequences. The research team studied a repeated genomic sequence called SINE B2, which is located on the growth hormone gene locus, the gene related to the aging process and longevity. The scientists were surprised to find that SINE B2 sequence is critical to formation of the functional domain boundaries for this locus.
Functional domains are stretches of DNA within the genome that contain all the regulatory signals and other information necessary to activate or repress a particular gene. Each domain is an entity unto itself that is defined, or bracketed, by a boundary, much as words in a sentence are bracketed by punctuation marks. The researchers’ data suggest that repeated genomic sequences might be a widely used strategy used in mammals to organize functional domains.
“Without boundary elements, the coding portion of the genome is like a long, run-on sequence of words without punctuation,” said Rosenfeld.
Decoding the information written in “junk” DNA could open new areas of medical research, particularly in the area of gene therapy. Scientists may find that transferring encoding genes into a patient, without also transferring the surrounding genomic sequences which give structure or meaning to these genes, would render gene therapy ineffective.
Contributors to the paper include Lluis Montoliu, Rosa Roy and Angel Garcia-Díaz of the Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología in Madrid, Spain; Christopher K. Glass, M.D., Ph.D., UCSD Department of Cellular and Molecular Medicine; Esperanza Núñez, Gratien G. Prefontaine, Bong-Gun Ju, Kenneth A. Ohgi, Kasey Hutt, Xiaoyan Zhu and Yun Yung, Howard Hughes Medical Institute, Department of Molecular Medicine, UCSD School of Medicine; and Thorsten Cramer, Division of Endocrinology, UCSD Department of Medicine.
The research was funded in part by the Howard Hughes Medical Institute and the National Institutes of Health.
Contact: Debra Kain
University of California – San Diego
Many otherwise healthy children and adolescents have low vitamin D levels, which may put them at risk for bone diseases such as rickets. African American children, children above age nine and with low dietary vitamin D intake were the most likely to have low levels of vitamin D in their blood, according to researchers from The Children’s Hospital of Philadelphia.
A study in the current issue of the American Journal of Clinical Nutrition measured blood levels of vitamin D in 382 healthy children between six years and 21 years of age living in the northeastern U.S. Researchers assessed dietary and supplemental vitamin D intake, as well as body mass, and found that more than half of the children had low blood levels of vitamin D. Of the subjects, 55 percent of the children had inadequate vitamin D blood levels and 68 percent overall had low blood levels of the vitamin in the wintertime.
“The best indicator of a person’s vitamin D status is the blood level of a vitamin D compound called 25-hydroxyvitamin D,” said Babette Zemel, Ph.D., a nutritional anthropologist at Children’s Hospital and primary investigator of this study. “Vitamin D deficiency remains an under-recognized problem overall, and is not well studied in children.”
Vitamin D is crucial for musculoskeletal health. The primary dietary source of the vitamin is fortified milk, but the best way to increase vitamin D levels is from exposure to sunshine. Severe deficits in vitamin D may lead to muscle weakness, defective bone mineralization and rickets. In addition to musculoskeletal effects, vitamin D is important for immune function, and low blood levels of the vitamin may contribute to diseases such as hypertension, cancer, multiple sclerosis and type 1 diabetes. Decreased blood levels of vitamin D have also been linked to obesity.
Further study is needed to determine the appropriate blood levels of vitamin D in children, said Dr. Zemel, who added that a review of the current recommendations for vitamin D intake is needed.
Grants from the National Institutes of Health and several private sources supported this study.
Dr. Zemel’s co-authors were Mary B. Leonard, M.D. and Virginia A. Stallings, M.D., of The Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, as well as Francis L. Weng and Justine Shults, also of the University of Pennsylvania School of Medicine.
About The Children’s Hospital of Philadelphia: The Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
Contact: Joey Marie McCool
Children’s Hospital of Philadelphia
Contact: Rachel Salis-Silverman
JAMA and Archives Journals
It is becoming more common for children with complex chronic conditions to die in their home than in a hospital, although black and Hispanic children with these conditions are less likely to die in their home, according to a study in the June 27 issue of JAMA, a theme issue on chronic diseases of children.
Chris Feudtner, M.D., Ph.D., M.P.H., of Children’s Hospital of Philadelphia, presented the findings of the study at a JAMA media briefing in New York.
Many pediatric palliative care clinicians suggest that the preferred place of death, by the family, of an infant, child, or adolescent with a medically complex chronic condition is the home. Advances in home-based medical technology and changes in attitudes about pediatric palliative care and hospice services may be making this a more viable option, according to background information in the article.
Dr. Feudtner and colleagues conducted a study to determine if the proportion of complex chronic condition-related deaths occurring at home among children and adolescents increased between 1989 and 2003, and to assess if there were any race and ethnicity disparities in the location of death. The researchers analyzed data from the National Center for Health Statistics’ Multiple Cause of Death Files.
Among the 22.1 percent of deaths (198,160 of 896,509 total deaths) attributed to a complex chronic condition between 1989 and 2003, the percentage of deaths occurring at home increased significantly for all age groups (overall, from 10.1 percent in 1989 to 18.2 percent in 2003), but with larger increases for deaths beyond infancy. The odds of death occurring at home increased by 3.8 percent annually.
The percentage of individuals dying at home increased significantly over time for infants (4.9 percent home deaths in 1989 to 7.3 percent in 2003); 1 to 9-year-olds (17.9 percent to 30.7 percent), and 10 to 19-year-olds (18.4 percent to 32.2 percent). During this same period, there was a significant decline in the percentage of deaths occurring in the hospital for each of these three age categories.
The authors suggest that this gradual change in place of death may be occurring because of advances in medical technology in the home setting and broad shifts in attitudes and decision-making processes regarding palliative and end-of-life care in U.S. culture.
The child’s race, ethnicity, and region of home residence were significantly associated with death occurring at home. The odds of dying at home were reduced by 50 percent among black individuals, and reduced by 48 percent among Hispanic individuals, when compared with whites.
Concerning possible reasons for the observed racial and ethnic differences, “ … differential access to health care services or medical technology, divergent cultural attitudes or approaches to palliative and end-of-life care decision making, or differing levels of financial or other support within the patient’s or family’s social network may make dying at home more or less likely.”
“… as efforts to improve understanding of the sources and remedies of racial and ethnic disparities in pediatric end-of-life care are completed, medical and other concerned professionals need to ensure that all patients have access to necessary care and that all dialogue and interactions regarding decisions about care—whether curative, life-extending, or palliative—are built on mutual understanding, trust, and respect,” the authors conclude.
(JAMA. 2007;297:2725-2732. Available pre-embargo to the media at http://www.jamamedia.org)
Editor’s Note: The conduct of this study was supported in part by grants from the Agency for Healthcare Research and Quality and the National Institute of Nursing Research of the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
For More Information: Contact the JAMA/Archives Media Relations Department at 312-464-JAMA or email: firstname.lastname@example.org.
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