(Press-News.org) Durham, NC - A new study reported in STEM CELLS reveals a unique population of skeletal stem cells (SSCs) that function during the transitional period between rapid bone growth and bone maintenance. This discovery provides an opportunity to determine whether alterations in the SSCs' pattern might affect bone formation, as well as helps us understand the physiological factors that regulate its timing.
"This is particularly important given that anything that interferes with the proper development of bone mass during childhood and adolescence has long-lasting effects on our health, including the development of osteoporosis in adults," said corresponding author Diana L. Carlone, Ph.D., of Boston Children's Hospital and the Harvard Stem Cell Institute.
The researchers came across this new information while investigating the role of mTert-expressing cells in postnatal mouse long bone. Postnatal bone formation relies on skeletal progenitor/stem cells. These cells also play a key role in repairing fractured or otherwise damaged bone. Tert (telomerase) is an enzyme found in the body's cells that helps keep cells alive by adding DNA to the ends of their chromosomes (telomeres). Each time a cell divides, its telomeres lose a small amount of DNA and become shorter. Tert activity prevents this aging process.
Recent lineage-tracing data indicate that SSC populations are regulated by time and spacing, with distinct populations functioning during bone growth and maintenance. In addition, growth-associated SSCs have been suggested as the predecessors to adult SSCs, implying that the SSC populations are highly complex and perhaps exist in hierarchies. There is strong interest in identifying stem cells within the skeleton, and much has been done to understand these cells in vitro ("in the test tube"); however, these findings are tempered by the fact that the lineage potential of cells in vitro can differ from their capacity in vivo (in the body).
"Going forward it will be imperative that markers and the cell populations they identify are validated in vivo before being accepted as an SSC population," Dr. Carlone said.
Previously, she and her team had shown that mTert expression marks embryonic stem cells, induced pluripotent stem cells and self-renewing tissue stem cells. Other researchers had proven that telomerase is necessary for SSC self-renewal and differentiation, and that a decline in telomerase activity in humans correlates with a decrease in bone homeostasis (stability), leading to osteoporosis. While all these studies indicate that telomerase is important for SSC function and bone homeostasis, what remained unclear was whether telomerase expression marks skeletal stem cells.
That's what the Carlone team set out to discover. They already knew that discrete SSC populations function during specific time periods corresponding to rapid bone growth and bone maintenance. To investigate whether mTert is expressed during these same periods, the Carlone team examined the long bones of an mTert mouse model they had developed, which recapitulates endogenous telomerase activity, specifically looking at what was happening at one, three and 12 weeks of age. To do this, they used quantitative (q) RT-PCR analysis (reverse transcription-polymerase chain reaction), which is the most sensitive technique for mRNA detection and quantitation currently available.
What they learned is that although mTert was detected at low levels during the multiple time points, it was upregulated at the age of weaning (three weeks), suggesting that mTert+ cells are temporally regulated and mark a discrete time period interposed between rapid bone growth and bone maintenance. They next looked at the location of the mTert-expressing cells at these same endpoints and were able to identify the mTert+ cells in regions known to house SSCs, including the fibrous tissue at the ends of long bones (the metaphyseal stroma), as well as in the growth plate and the bone marrow.
"We also show that mTert-expressing cells are a distinct SSC population with enriched colony-forming capacity and contribute to multiple mesenchymal lineages in vitro. In contrast, in vivo lineage-tracing studies identified mTert+ cells as osteochondral progenitors and contribute to the bone-forming cell pool during endochondral bone growth, with a subset persisting into adulthood," Dr. Carlone noted.
"Taken together, our results show that mTert expression is temporally regulated and marks SSCs during a discrete phase of transitional growth between rapid bone growth and maintenance that corresponds to the adolescent growth spurt in humans. We believe this warrants future studies focused on understanding how alterations in this cell population during this growth period translate into disorders such as osteoporosis."
"The temporal regulation of telomerase in the progenitor cells that form bone during adolescent growth is a very important advance in the understanding of bone development," said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. "This knowledge could also aid in understanding and improving regenerative therapies for bone injury and disease."
The full article, "Telomerase expression marks transitional growth-associated skeletal progenitor/stem cells," can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3318.
About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.
About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.
About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.
BINGHAMTON, NY -- A new leader takes office and foreign rivals begin to test the waters. How tough is this new leader? Are they willing to risk war, or just full of bluster?
This testing can escalate crises, increasing the risk of war as international adversaries gauge the new leader's willingness to use force. A new paper co-written by faculty at Binghamton University, State University of New York shows that when this "turnover trap" occurs depends a good deal on the politics back home, and the nature of the leader's transition into office.
Binghamton University Associate Professor of Political Science Amanda Licht was among ...
AURORA, Colo. (Jan. 13, 2021) - Mucus in the lungs can be fatal for asthma patients, but scientists at the University of Colorado Anschutz Medical Campus have broken up those secretions at the molecular level and reversed their often deadly impacts.
In a study published Monday in the journal Nature Communications, the researchers explained how they created an inhaled treatment that disrupted the production of excess mucus by reducing disulfide bonds in mice and opening up their airways. The same treatment had similar impacts on human mucus samples.
"Currently about 10% of the population has asthma," said the study's lead author Christopher Evans, PhD, professor of Pulmonary Sciences & Critical ...
A common bacterial species naturally infecting mosquitoes may actually be protecting them against specific mosquito pesticides, a study has found.
Wolbachia - a bacterium that occurs naturally and spreads between insects - has become more frequently used in recent years as a means of controlling mosquito populations.
Scientists at the University of Reading, and the INBIOTEC-CONICET and the National University of San Juan in Argentina, studied the effect of Wolbachia on a common mosquito species and found those carrying the bacteria were less susceptible to widely used pesticides.
Dr Alejandra Perotti, an Associate Professor in invertebrate biology at the University of Reading, and a co-author of the study, said: "This shows the importance of looking more ...
Without immediate and drastic intervention, humans face a "ghastly future" -- including declining health, climate devastation, tens of millions of environmental migrants and more pandemics -- in the next several decades, according to an international team of 17 prominent scientists. ...
Researchers at Linköping University, Sweden, have developed efficient blue light-emitting diodes based on halide perovskites. "We are very excited about this breakthrough", says Feng Gao, professor at Linköping University. The new LEDs may open the way to cheap and energy-efficient illumination.
Illumination is responsible for approximately 20% of global electricity consumption, a figure that could be reduced to 5% if all light sources consisted of light-emitting diodes (LEDs). The blue-white LEDs currently in use, however, need complicated manufacturing methods and are expensive, which makes it more difficult to achieve ...
Atomic nuclei are held together by the strong interaction between neutrons and protons. About ten percent of all known nuclei are stable. Starting from these stable isotopes, nuclei become increasingly unstable as neutrons are added or removed, until neutrons can no longer bind to the nucleus and "drip" out. This limit of existence, the so-called neutron "dripline", has so far been discovered experimentally only for light elements up to neon. Understanding the neutron dripline and the structure of neutron-rich nuclei also plays a key role in the research program for the future accelerator facility FAIR at the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt.
In a new study, "Ab Initio Limits of Nuclei," ...
The levels of small molecules called microRNAs (miRNAs) circulating in blood could help identify early on children with life-threatening forms of malaria, according to a study led by the Barcelona Institute for Global Health, an institution supported by "la Caixa" Foundation, in collaboration with the Manhiça Health Research Center (CISM) in Mozambique. The results, published in Emerging Infectious Diseases journal, could also help better understand the mechanisms underlying severe malaria.
Malaria mortality among young African children remains unacceptably high. To improve the outcome, it is important to rapidly identify and treat children with severe forms of the disease. ...
Associate professor Masaya Tamura, Kousuke Murai (who has completed the first term of his master's program), and their research team from the Department of Electrical and Electronic Information Engineering at Toyohashi University of Technology have successfully transferred power and data wirelessly through seawater by using a power transmitter/receiver with four layers of ultra-thin, flat electrodes. In the field of wireless power transfers, seawater behaves as a dielectric with extremely high loss, and achievement through capacitive coupling is difficult. Up until now, it had been thought that wireless power transfers could only be achieved through magnetic coupling. ...
Researchers from the University of Seville and the University of Pavia have identified a link between Amyotrophic Lateral Sclerosis (ALS) and the accumulation of DNA-RNA hybrids in the genome. The accumulation of these hybrids causes increased genomic damage and boosts genetic instability. This finding will make it possible to better understand the molecular basis of the disease, as well as to propose new solutions to curb it.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of the central nervous system, characterised by progressive degeneration ...
The descendants of regular wild-type bacteria can evolve to survive for a long time on metallic copper surfaces that would usually kill them within a few minutes. An international research team led by Martin Luther University Halle-Wittenberg (MLU) and the Bundeswehr Institute of Microbiology was able to produce these tiny survivalists in the lab and has been able to study them more closely. The team reports on its findings in Applied and Environmental Microbiology.
Bacterial infections are usually treated with antibiotics. However, in recent decades many pathogenic bacteria have developed an increasing tolerance to common drugs. So-called multidrug-resistant bacteria are of particular concern as ...