Scientists discover a new kind of blood vessel in our bones that could help treat arthritis

• Capillaries - trans-cortical vessels - penetrate the shell of long bones in mice
• Provide most of bones' blood supply and take immune cells out of their marrow
• Similar canals found in human bones but unclear if they transport immune cells 

A new kind of blood vessels in our bones has been discovered by scientists.

The newly-discovered capillaries - called trans-cortical vessels (TCVs) - penetrate the hard shell of bones in mice.

Researchers found they provide most of the blood supply to the bones.

They also act as a 'shortcut' by carrying immune cells from the bone marrow to the injured area of the body - rather than the cells having to be 'picked up' by blood as it enters one end of the bone, travel through bone marrow, and exit the other end.

When analysing humans, the scientists found we too have similar blood vessels in the larger bones of our bodies.

The researchers hope their finding will lead to the development of new therapies that use this blood flow and immune cell migration to help treat inflammatory conditions, such as osteoarthritis.      

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Scientists have unveiled a new kind of blood vessels in our bones (stock)

The research was carried out by the University Duisburg-Essen, Germany, and led by Dr Anika Grüneboom, from the institute for experimental immunology and imaging.

Human anatomy is rarely the subject of scientific breakthroughs, with most experts being confident the major organs and tissues have already been discovered.   

'It is really unexpected being able to find a new and central anatomical structure that has not been described in any textbook in the 21st Century,' Dr Matthias Gunzer, study co-author and head of the institute, said.

He told NewScientist: 'It’s totally crazy there are still things to find out about human anatomy – we have discovered blood vessels in a new place that we didn’t know about before.'In their discovery, the scientists injected a fluorescent marker into the long bones of mice.

Long bones are hard and dense - providing strength, structure and mobility. An example is the femur, or thigh bone.

WHAT IS OSTEOARTHRITIS?

Osteoarthritis - sometimes called 'wear and tear' - is a condition that occurs when the surfaces within joints become damaged.

Cartilage covering the ends of bones gradually thin over time, and the bone thickens, according to Arthritis Research UK.    

Around a third of people aged 45 years and over in the UK suffer from the condition. This equates to roughly 8.75 million people. At least 20 million are known to suffer in the US.

It is different to rheumatoid arthritis, a long-term illness in which the immune system causes the body to attack itself, causing painful, swollen and stiff joints.  

Replacement joints are often necessary for osteoarthritis patients, because the joint has been worn down and causes agonising pain.The bones were then examined under a fluorescence microscope and X-ray.

Results  - published in the journal Nature Metabolism - revealed long bones in mice are supplied with oxygen and nutrients by hundreds of newly-discovered capillaries along the entire bone shaft. 

When the researchers looked at small pieces of human thigh bone, they found the same - albeit thicker - blood vessels, however, it is unclear if these carry immune cells. 

Professor Gunzer himself even took part - lying in a scanner for six hours while it imaged his lower leg. 

The discovered capillaries connect the inner and outer membranes that surround bones.  

They are thought to play a critical role in helping to transport blood in and out of the bones' hard shell. 

This blood also found to be rich in immune cells, which the capillaries carry from the bone marrow to the circulation.

Up until now, blood was assumed to enter long bones via arteries at the bones' end or through the few vessels along the bones' shaft, before passing through bone marrow and exiting the other end. 

'This is too oversimplified and does not correctly reflect the true natural situation,' Professor Gunzer said.

The researchers believe TCV re-modelling could play a role in the healing of fractures. 

To better understand this, they are calling for studies that investigate what 'maintains' these capillaries. 

Keep Exercising Mind And Body

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Activity Tied To Cognition, Despite Brain Pathologies

Physical activity, motor skills independently correlated with reduced dementia

Higher levels of physical activity and motor abilities were independently associated with better cognition in older adults, even when brain lesions or biomarkers linked to dementia were present, a post-mortem study showed.

The study also showed no evidence that a more active lifestyle or better motor abilities modified associations between dementia pathologies and cognitive function, suggesting the cognitive reserve associated with activity may be unrelated to them, Aron Buchman, MD, of the Rush University Medical Center in Chicago, and colleagues wrote in Neurology.

“Physical activity may provide cognitive reserve to maintain function independent of accumulating brain pathologies,” Buchman told MedPage Today.

“Similar findings have been reported for late-life cognitive activities,” he added. “Together, these suggest that even in the absence of treatment for Alzheimer’s disease and related disorders, a more active lifestyle including physical and cognitive activities may help maintain cognition in older adults.”

Numerous observational studies have supported an association between physical exercise and reduced cognitive decline, but the mechanisms remain unknown, noted James Mortimer, PhD, of the University of South Florida in Tampa, and Yaakov Stern, PhD, of Columbia University in New York, in an accompanying editorial.

“The results of randomized trials of physical exercise suggest that exercise leads to increases in brain tissue, including in the hippocampus, where atrophy is an early and important finding in Alzheimer’s disease,” they wrote. One trial showed aerobic exercise led to increased levels of brain-derived neurotrophic factor (BDNF) and increased hippocampal volume; other studies suggested higher BDNF gene expression may help slow cognitive decline. “Alternatively, physical exercise itself might reduce brain pathology,” Mortimer and Stern added: mouse models have shown that higher physical activity levels reduce Alzheimer’s pathology accumulation.

The study drew on data from the Rush Memory and Aging Project, a community-based cohort of older adults who agreed to annual detailed clinical examination and brain donation at the time of death. The analysis included 454 participants with an average age at death of 91; 73% were female. A total of 191 participants had been diagnosed with dementia and 263 with no dementia.

The researchers incorporated 10 supervised motor performance tests to determine a global motor ability score and relied on continuous multi-day accelerometer recordings to monitor physical activity. Activity results were collected about 2 years before death and were measured in counts/day. The overall average was 156,000 counts/day, with participants without dementia averaging 180,000 counts/day, and people with dementia averaging 130,000 counts/day.

At autopsy, the researchers assessed brain tissue for:

• Alzheimer’s disease pathology (neuritic plaques, diffuse plaques, and neurofibrillary tangles)
• Nigral neuronal loss
• Lewy body disease pathology
• TAR DNA-binding protein 43
• Hippocampal sclerosis
• Macroscopic cerebral infarcts
• Cerebral atherosclerosis
• Microscopic cerebral infarcts
• Cerebral arteriolosclerosis
• Cerebral amyloid angiopathy

On average, participants had three different brain pathologies, with one or more pathologies observed in nearly all cases.

Buchman and colleagues performed regression analyses to “examine whether motor abilities or the quantity of daily physical activity attenuates the association of indices of AD pathology with the level of cognitive function proximate to death,” they wrote. Higher levels of total daily activity (estimate 0.148 ± 0.049, 95% CI 0.053–0.0.244, P=0.003) and better motor abilities (estimate 0.283 ± 0.055, 95% CI 0.175–0.390, P<0.001) both were independently associated with better global cognition proximate to death. These independent associations remained significant when interaction terms for Alzheimer’s disease and other pathologies were added.

Each standard deviation increase of total daily activity or motor capacity was associated with a reduction of dementia risk (total daily activity 31%; motor abilities 55%). These associations were additive, as the association of total daily physical activity with cognition did not vary with motor abilities.

“These data provide support for the idea that strategies or behaviors that lead to a more active lifestyle and better motor abilities may provide cognitive reserve, which may maintain cognitive function in older adults despite the accumulation of Alzheimer’s disease and other common brain pathologies,” the researchers wrote. “Further work is needed to clarify to what extent the risk factors and the types and duration of interventions to increase total daily physical activity and motor abilities are distinct and can be disentangled.”

The authors noted several limitations to their research: the data were cross-sectional and causal inferences cannot be drawn. It’s possible some of the association resulted from reverse causality (that lower cognitive function led to less activity). Accelerometers used in the study did not differentiate between various physical activities (such as steps vs arm movements) And the researchers assessed activity only at one point later in life; whether physical activity in early life may have played a role is unknown.

The study was supported by the National Institutes of Health, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund.

Buchman reported no disclosures relevant to the manuscript. Other researchers reported relationships with Grifols, Lilly, Genentech, the Michael J. Fox Foundation, and the National Hockey League.

Exercise DOES beat depression: Study finds evidence for long-held theory that running 15 minutes a day boosts mood

• For years, studies found a connection between working out and lower depression risk
• But there was no evidence to show a causal relationship
• Now researchers at Massachusetts General Hospital have found evidence for it

Scientists have found some concrete evidence that exercising a little bit every day does reduce depression symptoms and boost overall mood.

For years, studies have found a connection between working out and lower depression risk - we all know exercise releases endorphins and endorphins make you happy.

But until now, there was no evidence to show a causal relationship when it came to depression - whether physical activity really did affect the condition, or simply that people with depression exercised less.

Now, a study by researchers at Massachusetts General Hospital (MGH) has presented evidence based on genetic data showing that working out is beneficial - and found no evidence that depression affects your ability to work out.

The team says the findings could help doctors and officials to develop prevention strategies for the growing number of people battling symptoms of depression.  

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For years, studies found a connection between working out and lower depression risk. But there was no evidence to show a causal relationship. Now researchers at MGH have found evidence for it

'On average, doing more physical activity appears to protect against developing depression,' says Karmel Choi, PhD, of the Psychiatric and Neurodevelopmental Genetics Unit in the MGH Center for Genomic Medicine, lead author of the report.

'Any activity appears to be better than none; our rough calculations suggest that replacing sitting with 15 minutes of a heart-pumping activity like running, or with an hour of moderately vigorous activity, is enough to produce the average increase in accelerometer data that was linked to a lower depression risk.' 

WHY RESEARCHERS HAVE STRUGGLED TO CONNECT THE DOTS - BUT GENES COULD OFFER AN ANSWER

Epidemiology is the study of what causes health outcomes and disease, and how to control them. 

But very often the things we're trying to understand - why some people love to drink  alcohol, what causes anxiety, who is at higher risk for certain cancers - are hard to measure clearly. 

Most studies end up being observational. In other words, scientists track their variables - in this case, physical activity levels and depression diagnoses - to see if the theory matches up. 

However, that is very rarely enough to determine a causal relationship. Even if you try to account for all the variables again and again, there will still be a gap in your data.

In a bid to dig deeper, and to eliminate one of the biggest question marks, the MGH team employed a popular technique: using genes as a framework.     

Both depression and physical activity can be affected by our genes. Some people are more naturally athletic, some are more prone to depression. 

Using genomic data, we can stabilize that factor. We can determine whether people with depression are simply just less active, or not. 

The technique (known as Mendelian randomization) is not a silver bullet; you are still left with room for other explanations. But it gets us as close as possible to confirming a cause. 

They pooled data from the UK Biobank and a global research group.   

For physical activity, they had two pools of results: one in which 377,000 people reported their own physical activity, and another in which 91,000 people wore fitness trackers to monitor their movement. This was compared to genetic tests. 

For depression, they analyzed the genetic makeup of 143,000 who were diagnosed with depression.  

The results of the Mendelian randomization study found no connection between self-reported activity and lower rates of depression. 

But when they looked at data from the fitness trackers, they did see improvement: those who worked out regularly had fewer symptoms of depression. 

The researchers said there is a myriad of easy explanations for that gap. Firstly, our memories are not always perfectly accurate, and sometimes we are driven to slightly curate our own version of what happened. Secondly, and crucially, many may not count everyday movement, such as climbing the stairs or walking to the subway, as exercise, whereas a fitness tracker would. 

They found nothing to suggest depression could hamper physical activity, nor that people with depression were less physically capable.   

Senior author Jordan Smoller, MD, ScD, director of the Psychiatric and Neurodevelopmental Genetics Unit and a professor of Psychiatry at Harvard Medical School, says that gene variants do not determine a person's behaviors or outcomes.

However, he says: '[T]heir average associations with certain traits in these very large studies can help us look at a question such as whether physical activity - or the tendency to engage in more physical activity - has a likely causal effect on depression. 

'And the answers to those questions could help researchers design large-scale clinical trials.'

Choi adds: 'And of course it's one thing to know that physical activity could be beneficial for preventing depression; it's another to actually get people to be physically active. 

'More work needs to be done to figure out how best to tailor recommendations to different kinds of people with different risk profiles. 

'We currently are looking at whether and how much physical activity can benefit different at-risk groups, such as people who are genetically vulnerable to depression or those going through stressful situations and hope to develop a better understanding of physical activity to promote resilience to depression.'