EDITOR'S PICK: Controlling bone formation to prevent osteoporosis
Aging disrupts the balance between bone formation and bone destruction, resulting in osteoporosis, which is characterized by reduced bone mass and increased risk of fracture. Recent data have suggested that this imbalance is a result of a decrease in formation of bone forming osteoblast cells from mesenchymal cells upon aging. Instead, these cells form more fat cells. Insight into this age-related switch in cell type generation has now been provided by a team of researchers, led by Hiroshi Takayanagi, at Tokyo Medical and Dental University, Japan, working in mice. The data generated might provide new avenues of research for those developing approaches to treat age-related osteoporosis.
In the study, the gene regulatory protein Maf was found to promote mesenchymal cell generation of osteoblasts and suppress their generation of fat cells. Consistent with this, mice lacking Maf showed delayed bone formation. Furthermore, Maf levels were found to decrease in mouse mesenchymal cells upon aging and to be reduced by increased oxidative stress, something that occurs upon aging. Both the authors and, in an accompanying commentary, Laurie McCauley, at University of Michigan, Ann Arbor, believe these data could lead to new approaches to treat age-related osteoporosis.
TITLE: Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation
AUTHOR CONTACT:
Hiroshi Takayanagi
Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Phone: 81.3.5803.5471; Fax: 81.3.5803.0192; E-mail: taka.csi@tmd.ac.jp.
View this article at: http://www.jci.org/articles/view/42528?key=d12e4d8ca78f26b68ab5
ACCOMPANYING COMMENTARY
TITLE: c-Maf and you won't see fat
AUTHOR CONTACT:
Laurie K. McCauley
University of Michigan, Ann Arbor, Michigan, USA.
Phone: 734.647.3206; Fax: 734.763.5503; E-mail: mccauley@umich.edu.
View this article at: http://www.jci.org/articles/view/44786?key=e9e9d82df06ab0518231
IMMUNOLOGY: Defective immune cells in patients with type 1 diabetes
Studies in mice have defined a subset of immune cells known as HLA-E–restricted CD8+ suppressor (or regulatory) cells as having a role in ensuring that the immune system responds to invading microbes but does not turn on the body to cause autoimmune disease. Now, Hong Jiang and colleagues, at Columbia University, New York, have identified the same cells in humans. Interestingly, these cells were defective in the majority of patients with type 1 diabetes that the authors studied. As the defective HLA-E–restricted CD8+ cells could be rendered functional in vitro with the appropriate stimulation, the authors suggest that these cells might be a viable target for treating individuals with type 1 diabetes. This sentiment is echoed by Luc Van Kaer, at Vanderbilt University School of Medicine, Nashville, in an accompanying commentary.
TITLE: HLA-E–restricted regulatory CD8+ T cells are involved in development and control of human autoimmune type 1 diabetes
AUTHOR CONTACT:
Hong Jiang
Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Phone: 212.305.6979; Fax: 212.305.4943; E-mail: hj4@columbia.edu.
View this article at: http://www.jci.org/articles/view/43522?key=b86c26a3952f29cbfffb
ACCOMPANYING COMMENTARY
TITLE: Comeback kids: CD8+ suppressor T cells are back in the game
AUTHOR CONTACT:
Luc Van Kaer
Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Phone: 615.343.2707; Fax: 615.343.2972; E-mail: luc.van.kaer@vanderbilt.edu.
View this article at: http://www.jci.org/articles/view/44395?key=ce025fb979c94e36a50b
METABOLIC DISEASE: Immune cells known as macrophages act as weight loss aids
Individuals who are obese are at increased risk of becoming resistant to the effects of the hormone insulin and consequently of developing type 2 diabetes. One factor contributing to the development of insulin resistance in individuals who are obese is the accumulation of immune cells known as macrophages in white fat tissue. New research, led by Anthony Ferrante Jr., at Columbia University, New York, has now shown in mice that weight loss is unexpectedly also associated with rapid, albeit transient, recruitment of macrophages to white fat tissue. Macrophage recruitment in this context seem to be driven by high levels of free fatty acids (the building blocks of fats) released by breakdown of fats in fat tissue. Furthermore, the recruited macrophages soak up the broken down fats, leading the authors to suggest that they buffer local increases in released fat as fat tissue breaks down during weight loss.
Ajay Chawla and Alex Red Eagle, at Stanford University, Stanford, discuss these surprising data in an accompanying commentary.
TITLE: Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue
AUTHOR CONTACT:
Anthony W. Ferrante, Jr.
Columbia University, New York, New York, USA.
Phone: 212.851.5322; Fax: 212.851.5335; E-mail: awf7@columbia.edu.
View this article at: http://www.jci.org/articles/view/42845?key=4bdf5e878aea01111c81
ACCOMPANYING COMMENTARY
TITLE: In obesity and weight loss, all roads lead to the mighty macrophage
AUTHOR CONTACT:
Ajay Chawla
Stanford University School of Medicine, Stanford, California, USA.
Phone: 650.724.4022; Fax: 650.725.7085; E-mail: achawla@stanford.edu.
View this article at: http://www.jci.org/articles/view/44721?key=2c3e550f18197d74d358
CARDIOLOGY: New level of control for the heart beat
The heart beat, nerve cell communication, and skeletal muscle function are all controlled by channels in the cell membrane that regulate the movement of sodium ions (Na+). Mutations in these so called voltage-gated Na+ channels result in forms of epilepsy and heart conditions such as long QT syndrome that are characterized by an irregular heart beat. New research, conducted by a team of investigators led by Peter Mohler and Thomas Hund, at the University of Iowa Carver College of Medicine, Iowa City, has now identified a multifunctional regulatory platform for voltage-gated Na+ channels in mice.
In the study, the structural protein beta-IV-spectrin was found to be part of the multi-protein complex containing the predominant voltage-gated Na+ channel in heart muscle cells in mice. Further, beta-IV-spectrin recruited to the multi-protein complex the protein CaMKII, which in turn modified the voltage-gated Na+ channel, modulating its function. In the presence of mutant forms of beta-IV-spectrin, the function of the voltage-gated Na+ channel in the heart was impaired and the mice exhibited an abnormal heart beat. As discussed by Robert Kass and Kevin Sampson, at Columbia University, New York, in an accompanying commentary, these data provide new insight into the control of the heart beat and might provide new therapeutic targets.
TITLE: A beta-IV-spectrin/CaMKII signaling complex is essential for membrane excitability in mice
AUTHOR CONTACT:
Peter J. Mohler
University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Phone: 319.335.9691; Fax: 319.353.5552; E-mail: peter-mohler@uiowa.edu.
Thomas J. Hund
University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Phone: 319.384.1167; Fax: 319.353.5552; E-mail: thomas-hund@uiowa.edu.
View this article at: http://www.jci.org/articles/view/43621?key=360f9b42c37450b2ca5f
ACCOMPANYING COMMENTARY
TITLE: Location, location, regulation: a novel role for beta-spectrin in the heart
AUTHOR CONTACT:
Robert S. Kass
Columbia University, New York, New York, USA.
Phone: 212.305.3720; Fax: 212.305.3545; E-mail: rsk20@columbia.edu.
View this article at: http://www.jci.org/articles/view/44810?key=fa2a861e4ec9dbcfa5d0
Journal
Journal of Clinical Investigation