Breaking News
February 17, 2019 - Support from trusted adults can reduce risk of dying in suicidal teens, finds study
February 17, 2019 - Heart attack awareness improved since 2008
February 17, 2019 - Exercise gives a better brain boost to older men than women
February 17, 2019 - New research disproves previous assumptions of how looks influence personality
February 17, 2019 - Cannabis use as a teenager linked to depression later in life
February 17, 2019 - Sinks by Toilets in ICU Patient Rooms Harbor Harmful Bacteria
February 17, 2019 - Cancer cells’ plasticity makes them harder to stop
February 17, 2019 - Young cannabis users have increased risk of depression and suicidal behavior
February 17, 2019 - Tasmanian Devils Likely to Survive Cancer Scourge
February 17, 2019 - Neoadjuvant PD-1 blockade seems effective in glioblastoma
February 17, 2019 - Personal, social factors play role in enabling sustainable return to work after ill health
February 17, 2019 - Mouse studies show ‘inhibition’ theory of autism wrong
February 17, 2019 - Study shows how neuroactive steroids inhibit activity of pro-inflammatory proteins
February 17, 2019 - Use of liver grafts from older donors decreased despite better outcomes in recipients
February 17, 2019 - MUSC researchers discover new mechanism for a class of anti-cancer drugs
February 17, 2019 - HPV misconceptions are causing women to miss smear tests
February 17, 2019 - Sanofi and Regeneron Offer Praluent (alirocumab) at a New Reduced U.S. List Price
February 17, 2019 - Researchers say auditory testing can identify children for autism screening
February 17, 2019 - New method analyzes how single biological cells react to stressful situations
February 17, 2019 - WVU gynecologic oncologist investigates novel treatment for cervical and vaginal cancers
February 17, 2019 - ADHD diagnoses poorly documented
February 17, 2019 - Majority of gender minority youth do not identify with traditional sexual identity labels
February 17, 2019 - AbbVie, Teneobio enter into strategic transaction to develop potential treatment for multiple myeloma
February 17, 2019 - Lower Birth Weight May Up Risk for Psychiatric Disorders
February 17, 2019 - Scientists identify reversible molecular defect underlying rheumatoid arthritis
February 17, 2019 - Moffitt researchers shed light on how CAR T cells function mechanistically
February 16, 2019 - Female Anatomy May Play Big Role in Sperm’s Success
February 16, 2019 - BMI may mediate inverse link between fiber intake, knee OA
February 16, 2019 - Movement impairments in autism can be reversed through behavioral training
February 16, 2019 - Studies address racial disparities in postpartum period and cardiovascular health
February 16, 2019 - Scientists implicate hidden genes in the severity of autism symptoms
February 16, 2019 - Decreased deep sleep linked to early signs of Alzheimer’s disease
February 16, 2019 - Neuroscientists show how the brain responds to texture
February 16, 2019 - Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
February 16, 2019 - What Can I Do About Sweating? (for Teens)
February 16, 2019 - Companies navigate dementia conversations with older workers
February 16, 2019 - Newly developed stem cell technologies show promise for treating PD patients
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Children with ASD more likely to face maltreatment, study finds
February 16, 2019 - Study finds genetic vulnerability to use of menthol cigarettes
February 16, 2019 - Promising drug developed to rejuvenate muscle cells
February 16, 2019 - H-RT should be the standard of care for men with low risk prostate cancer, study shows
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
Key signaling molecule that helps stem cells make healthy bone declines as we age

Key signaling molecule that helps stem cells make healthy bone declines as we age

image_pdfDownload PDFimage_print

With age, expression of a small molecule that can silence others goes way up while a key signaling molecule that helps stem cells make healthy bone goes down, scientists report.

They have the first evidence in both mouse and human mesenchymal stem cells that this unhealthy shift happens, and that correcting it can result in healthier bone formation.

The small molecule is microRNA-141-3p and the signaling molecule is stromal-cell derived factor, or SDF-1, they report in the Journal of Gerontology: Biological Sciences.

“If you are 20 years old and making great bone, you would still have microRNA-141-3p in your mesenchymal stem cells. But when you are 81 and making weaker bone, you have a lot more of it,” says Dr. Sadanand Fulzele, bone biologist in the Department of Orthopaedic Surgery at the Medical College of Georgia at Augusta University.

Restoring a more youthful balance could be a novel strategy for reducing age-associated problems likes osteoporosis and the impaired ability to heal bone breaks, says Fulzele, a corresponding author on the study.

“You want it sort of in that sweet spot,” says Dr. William D. Hill, a longtime stem cell researcher at MCG now on the faculty at the Medical University of South Carolina. “What we are trying to do is dial it back down from where it’s being overexpressed due to factors like aging and oxidative stress and suppression of estrogen, and bring it back into a range that would effectively allow more normal bone formation,” says Hill, also a corresponding author.

About 30 percent of postmenopausal women in the United States and Europe have osteoporosis, according to the International Osteoporosis Foundation. At least 40 percent of these women and 15-30 percent of men will sustain one or more fractures in their lifetime, the foundation says, and one fracture puts them at increased risk for others.

Mesenchymal stem cells can differentiate into the major components of our skeleton: bone-forming osteoblasts; actual bone cells or osteocytes, made by osteoblasts; cartilage-cells called chondrocytes; as well as fat cells, or adipocytes.

SDF-1 is a key signaling molecule that helps regulate the differentiation of stem cells into these cells, the MCG research team has shown. SDF-1 has a myriad of other roles as well, including helping mesenchymal stem cells get to the right spot during bone formation and bone repair and protecting cells from the ravages of oxidative stress.

It was SDF-1’s clear significance in bone health – and the fact that it declines with age – that got the scientists interested in how it’s regulated. They hypothesized that decreasing SDF-1 is at least one way microRNA-141-3p impacts healthy differentiation of mesenchymal stem cells.

They suspected microRNA-141-3p as a culprit because Fulzele had already found it suppresses a transporter of vitamin C, which enables the vitamin to reach our cells once we eat foods like kale and Brussel sprouts. Vitamin C also is important for bone health, and without sufficient transporters, the vitamin instead starts to accumulate outside the cell where it generates destructive oxidative stress. The scientists also had already found it could hinder that important differentiation of mesenchymal stem cells and knew levels of microRNA-141-3p increase with aging. Their animal studies had indicated that oxidative stress in mesenchymal stem cells decreases SDF-1 and that the signaling molecule could protect those cells from death by oxidative stress.

Now putting the pieces together they speculated – and have found – that higher oxidative stress elevates microRNA-141-3p expression, which in turn decreases SDF-1 levels.

In both mice and human mesenchymal stem cells, they found levels of microRNA-141-3p were low in young cells but levels were tripled or more in older cells. They found essentially the opposite for SDF-1 levels.

When they injected a microRNA-141 mimic inside the stem cells, it essentially created a model of aging and SDF-1 levels again went down. Consequences of that included another shift that normally occurs with age as we make more bone-eating osteoclasts than bone-forming osteoblasts. The shift also resulted in mesenchymal stem cells making instead more fat, which they tend to do with age because it’s easier.

As part of testing their hypothesis from all directions, the scientists also added microRNA-141-3p to cells and watched bone function get worse, then used the inhibitor again and saw improvement.

Clinical-grade drugs, like the research drug they used to inhibit microRNA-141-3p and that might target other members of the micro-RNA 141 family as well, could one day be an effective way to help mesenchymal stem cells remain focused on making bone in the face of age and other conditions, Fulzele says.

At least in their cell studies: “It normalizes bone function. We think clinical-grade inhibitor may help us do the same in people,” the bone biologist says.

Hill says that a patch of endogenous or synthetic RNA could also be an option for precisely targeting errant microRNAS, which are usually the molecules doing the regulating.

They are now looking to move into animal models and look at a wide array of other factors like what happens to fat production, and can they improve fracture healing in a model of aging and/or prevent or at least reduce osteoporosis. Fulzele also wants to know if higher physical activity levels, which tend to diminish with age, can also help restore a healthier balance of microRNA-141-3p and SDF-1.

They also are looking at other members of the microRNA-141 family and how/if they interact with other family members to cause problems as we age, Hill says.

“We have identified a number of microRNAs that change in the bone marrow stem cells with aging and we are going after each one of these to understand how they are working and are they working together or independently,” Hill adds. “We are starting to take more of a biological systems approach, not just changing one target molecule, but looking at how this network of molecules is changed with age or disease and how we can reach in and sort of reset these different pathways.”

The scientists note that other genes also could be targets for this microRNA, since these molecular regulators typically target more than one gene.

Fulzele suspects lower levels of microRNA-141-3p in youth actually help fine-tune healthy bone formation – like a tiny turn of your radio dial would – and that it’s the high levels that make it bad for bone.

Even normal, healthy aging results in increased levels of oxidative stress, which includes things like reactive oxygen species that are byproducts of oxygen use.

The human stem cells the scientists isolated and analyzed came from 18-40 year olds and 60-85 year olds who had orthopaedic surgery.

Tagged with:

About author

Related Articles