Category: Skeletal System

Categories : Skeletal SystemTags :

Bone Cells Growing on Biomaterials Like Curvatures the Best

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TU Delft engineers have shown that the curvature of biomaterials inhibits or stimulates bone cells to make new tissue. Their findings are reported in Nature Communications, and their study of geometries could be an important step in research into repairing damaged tissues.

Living cells can perceive and respond to the geometry of their environment. “Cells sense and respond to the geometry of the surfaces they are exposed to. Depending on their curvature, surfaces can either encourage cells to create new tissue or prevent them from doing so,” says Amir Zadpoor, professor of Biomaterials and Tissue Biomechanics, supervisor of the study. “Stimulating curvatures made by a 3D printer are an easy and safe way to promote tissue growth. As compared to drugs, they are also much cheaper.”

The researchers grew bone cells in vitro surrounded by small moulds made from biomaterials with which the researchers have experience. Depending on the curvatures in the moulds, the cells tended to grow, divide, and form tissue to different extents.

Cells like a saddle shape

Although curved shapes seem to exist in endless variations, they always fall roughly into one of these three categories: a ball that has a convex curvature, a saddle that has a concave curvature, and a plate that is flat. One of the authors, assistant professor of Biomaterials Lidy Fratila-Apachitei: “Cells prefer a saddle shape. If they perceive a saddle shape nearby, growth is stimulated. The study also shows that cells prefer valleys over hills.”

Rather aligned than bent

First author Sebastien Callens did the experiments and analysis in the study. “Cells also have a skeleton, which consists of fibres that are under tension to different degrees. How tension builds up in those fibres strongly influences the behaviour of cells. Our study shows that cells collectively align their stress fibres with the curvatures they experience to minimise their need to bend. I could see that cells prefer to align than to bend.”

Budget of saddle curvature

You can’t have only saddle curves around cells. Just as the three angles of a triangle always add up to 180 degrees, the sum of all curvatures must also equal some fundamental numbers. “You always have a limited budget of saddle shapes,” says Zadpoor. “If you use too much negative curvature somewhere, you must use positive curvatures somewhere else to keep the sum constant. You need to use your budget wisely to encourage maximum tissue regeneration.”

New biomaterials

The study provides guidance on the optimal geometry of biomaterials and implants to maximise tissue regeneration. The complex geometric designs required are made using high-precision 3D printing techniques to make the shapes so small that they are perceptible to cells. Callens: “We have now discovered new playing rules by which biomaterials can stimulate tissue growth. In follow-up research, we will try to apply those rules optimally.”

Source: Delft University of Technology

Categories : Cancer Skeletal SystemTags :

Bone Matrix Protein Discovery could Yield New Osteosarcoma Treatments

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A study published in the Journal of Orthopaedic Research has identified a bone matrix protein called Secreted phosphoprotein 24 kD (Spp24) that may help to treat osteosarcoma, the most common type of bone cancer.

In experiments conducted in cells and mice, investigators found that Spp24 inhibits the proliferation and invasiveness of osteosarcoma tumour cells and promotes their apoptosis, or death. Mechanistically, Spp24 binds to and neutralises a protein called bone morphogenetic protein 2, which has tumour-enhancing properties.

“Spp24 and its proteolytic products have a number of effects on bone metabolism that have been elucidated to various degrees. They have the potential to be engineered into bone therapeutics, and this anti-tumour effect through bone morphogenetic protein 2 sequestration is only one such example,” said co–corresponding author Haijun Tian, MD, PhD, of Shanghai Jiao Tong University School of Medicine. “Like many other bone matrix proteins, the more we look into the function of Spp24, the more surprising roles we find even though the primary function of Spp24 remains uncertain.”

Source: Wiley

Categories : Ageing Skeletal SystemTags :

Bone Tissue has Lymphatic Vessels – and They Aid Healing

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To date, it has been assumed that bones lack lymphatic vessels, but new research published in the journal Cell not only mapped them within bone tissue, but demonstrated their role in bone and blood cell regeneration and reveals changes associated with ageing.

The network of vessels that form the lymphatic system plays an important role in draining excess fluid from tissues, clearing waste products and supporting immune responses.

The fine network of lymph vessels extends throughout the body, but a small number of sites such as the brain, eye and bone were previously assumed to lack lymph tissue. The hard tissue of bone in particular has traditionally made studying the distribution and role of blood and lymph more difficult.

Researchers used light-sheet imaging to identify and visualise the lymphatic vessels of bone in high-resolution 3D, revealing an active network of lymph vessels within bone. The researchers further identified some of the key signals happening between lymph vessels, blood stem cells and bone stem cells.

Dr Lincoln Biswas, co-first author of this study, said: ‘Interestingly after injury, lymphatic vessels in bone show dynamic crosstalk with blood stem cells and with specialised perivascular cells in order to accelerate bone healing. Such interactions between lymphatics and bone stem cells can harnessed to promote bone healing such as in fracture repair.’

The researchers found that lymphatic vessels in bone increase during injury via a signalling molecule called IL6, and trigger expansion of bone progenitor cells by secreting a different signal, called CXCL12. Dr Junyu Chen, a co-first author of the study now based at Sichuan University said: “Ageing is associated with diminished capacity for bone repair, and our findings show that lymphatic signalling is impaired in aged bones. Remarkably, the administration of young lymphatic endothelial cells restores healing of aged bones, thus providing a future direction to promote bone healing in elderly.”

Dr Anjali Kusumbe, who led the research said: “I am very excited as these findings not only demonstrate that lymphatic vessels do exist in bone but also reveal their critical interactions with blood stem cells and perivascular bone stem cells after injury to promote healing, thereby presenting lymphatics as a therapeutic avenue to stimulate bone and blood regeneration. Further, these findings are very fundamental, opening doors for understanding the impact of bone lymphatics on the immune system and their role in bone and blood diseases.”

Source: Oxford University

Categories : Skeletal SystemTags :

Excessive Physical Activity May Impact Teens’ Leg Development

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A study published in the Journal of Orthopaedic Research showed that physical activity levels may impact adolescents’ and young adults’ leg alignment during development, as measured by magnetic resonance imaging (MRI) scans.

The study included 57 elite male soccer players compared with 34 male and 34 female controls aged 11–21 years. Outcome measures were the hip knee angle (HKA), medial proximal tibial physeal angle (MPTPhyA), lateral distal femoral physeal angle (LDFPhyA) on full leg length MRI scans, and a physical activity questionnaire score.

Using magnetic resonance imaging scans, physical activity levels were associated with the development of varsus or ‘knock knees’, an abnormal leg alignment, which may represent a physiological adaptation to load where the shin bone meets the knee.

“Our study suggests that abnormal leg alignment, a risk factor for future injury and osteoarthritis, develops in early adolescence due to high activity levels,” said corresponding author Scott Fernquest, DPhil, of the University of Oxford. “Modifying activity levels during this critical period of growth may prevent the development of abnormal leg alignment. We hope our findings lead to further research investigating this possibility.”

Source: Wiley

Categories : Skeletal SystemTags :

Weight Loss Protects against Structural Defects of Knee Osteoarthritis

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Researchers conducting long-term follow ups of adults given knee X-rays found that a decrease in body mass index (BMI) was associated with both a lower incidence of the structural defects of knee osteoarthritis. Published in Arthritis & Rheumatology, also found reduced odds of these defects progressing.

In the study radiographic analyses were conducted of adults’ knees with and without the structural defects of knee osteoarthritis at baseline and at 4 to 5 years’ follow up from adults. A total of 9683 knees (from 5774 individuals) were assessed in an ‘incidence cohort’ along with 6075 knees (from 3988 individuals) in a ‘progression cohort.’

The researchers observed that a 1-unit drop in BMI was linked to a 4.76% reduction in odds of the incidence and progression of knee osteoarthritis. A 5-unit BMI drop, which can downgrade a BMI category (eg, from overweight to normal), reduced the odds of incidence and progression by 21.65%.

“These findings could be empowering for people with or at risk of knee osteoarthritis,” said lead author Zubeyir Salis, BEng, and a PhD student for Public Health at the University of New South Wales in Australia. “The current prevailing view is that knee osteoarthritis is part of ageing and that we have no control over it. However, my analyses suggest that some people could potentially prevent, slow or delay knee osteoarthritis by losing weight.”

Source: Wiley

Categories : Ageing Skeletal SystemTags :

Osteoporosis in Men is Often Overlooked

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Osteoporosis in men is often overlooked by health care professionals, found the authors of a review published in The Lancet Diabetes and Endocrinology. There is a desperate need for raising awareness of the condition in men to help improve outcomes for patients, the authors said.

Women are generally at higher risk of developing osteoporosis, as their bone density declines more rapidly than men at an earlier age, especially post-menopause. In most populations, men have larger and stronger bone and joint surfaces, so they can be overlooked when diagnosing the condition.

Reviewing available data on the condition in men, researchers found that they are generally diagnosed later, comply with treatment less and present to hospital in older ages than women. With fatality rates from hospitalisations with fragility fractures, like a broken hip, being higher than women.

The review’s author, Dr Tatiane Vilaca, said: “Generally diagnosis of osteoporosis happens when a patient presents at hospital with some kind of fragility fracture in older age, for example falling from standing height, and breaking a hip, wrist or spine.

“Research suggests men hospitalised with hip fractures tend to be older than women, which could be because the condition develops more slowly in men. As older people are usually slightly frailer, with poorer states of overall health, this could explain the slightly higher levels of disability and mortality associated in men with osteoporosis who are hospitalised following a fracture.”

The review found that although there is a lack of research about which treatment options are most effective in men, diagnosis and treatment options are effective.

The team believe further research specifically tailored to osteoporosis in male patients will help improve current diagnosis systems, helping clinicians with earlier diagnosis, and a focus on education for patients will support compliance with drug treatment programs, all improving outcomes for men living with osteoporosis.

Dr. Richard Eastell, Professor of Bone Metabolism at the Department of Oncology and Metabolism, said: “As women make up larger numbers of people living with osteoporosis, the data we have on the progression of the condition in men is currently not as robust. This updated review shows that further studies of male patients could help improve current diagnosis systems, as well as resources for the education of primary care clinicians and the general public on the early warning signs of osteoporosis in men.”

Dr. Vilaca added: “Despite the current gap in knowledge, men can still easily be screened for osteoporosis at their general practitioner surgery.

“Anyone with a family history of osteoporosis, broken bones, or fractures, those with acute back pain or a loss of height should be encouraged to have a check-up.

“These are all early warning signs of the condition in both men and women, and early preventative treatment is the best way to ensure a slower disease progression and longer, healthier life without a fracture.”

Source: University of Sheffield

Categories : Ageing Skeletal SystemTags :

Prunes Also Protect Bone Health in Men

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New research published in the Journal of Food and Medicine reports that daily prunes consumption protects bone health in men over 50. This study is the first of its kind to examine the beneficial prune effect on bones in men. 

Some 2 million men are estimated to be battling osteoporosis and another 16.1 million men have osteopenia, or low bone mass. Despite these numbers, bone disease in men is often overlooked.

“We’ve already seen significant evidence that prunes have a positive effect on bone health in women, so it’s particularly exciting to find that prunes can also play a beneficial role in men’s bone health. We look forward to continuing to study the ‘prune effect’ on bone and other health outcomes in men,” said lead researcher Professor Shirin Hooshmand at San Diego State University.

In this study, 57 healthy men aged 50-79 years old were randomised to either consume 100 grams of prunes every day or no prunes for twelve months. After a year, the prune consumers showed significant decreases in biomarkers of bone breakdown, while no changes were observed in the control group. The study authors also reported the men who ate prunes showed improvements in bone geometry indicating greater bone strength.

Historically, research has focused on osteoporosis and bone health in women, already indicating a favorable bone response to prunes specifically among postmenopausal women. Several studies have suggested that eating 50 to 100 grams of prunes everyday could lead to increased bone mass and decreased bone breakdown. Moreover, a recent case study earlier this year reported that total bone mineral density increased in a postmenopausal woman with osteopenia after she consumed 50 grams of prunes daily for 16 months.

“Bone health is not just a concern for women. Men need to think about how to protect their bones as well,” said Leslie Bonci, MPH, RDN and consultant with the California Prune Board. “Prunes are a shelf-stable and nutrient-packed food that provide a preventive, proactive, palatable option for men to optimize their bone health.”

While San Diego State University’s newest research is an exciting addition to existing prune-focused literature, more work on the effect of prunes on human bone health is currently underway. An upcoming study from Pennsylvania State University examines how consuming different amounts of prunes affects health outcomes in postmenopausal women over a one-year period. The study not only explores the impact of prunes on bone health, but it will also look at the prune-effect on inflammation and gut health.

Source: PR Newswire

Categories : Skeletal SystemTags :

How Osteocytes Form Their Networks of Dendrites

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Embedded within bone tissue are osteocytes, and the tree-like communication cells known as dendrites. Loss of dendrites to ageing contributes to bone fragility and osteoporosis. 

A study published in Nature Communications has revealed how osteocytes form dendrites – a discovery that might yield strategies to maintain these projections and therefore help maintain people’s bone health throughout their lives.

In their study, the researchers found that deletion of Sp7, a gene linked to both rare and common skeletal diseases, in osteocytes causes severe defects in osteocyte dendrites. This gene codes for a protein called a transcription factor, which controls the expression of other genes. The team found that the Sp7 transcription factor targets a gene called osteocrin, which promotes osteocyte dendrite formation. In mice, activating the osteocrin gene made up for the absence of Sp7 and reversed defects in osteocyte dendrites.

“In this work, we demonstrate key roles for the transcription factor Sp7 and its target osteocrin in orchestrating a gene regulatory network needed to promote healthy connections between bone cells,” said senior author Marc Wein, MD, PhD, an investigator in the endocrine unit at MGH and an assistant professor of medicine at Harvard Medical School. “Understanding how osteocytes maintain this network of connections opens up exciting possibilities for new ways to treat osteoporosis and other diseases where bones are prone to fracture.”

Source: Massachusetts General Hospital

Categories : Medical Research & Technology Skeletal SystemTags :

Atmospheric Plasma Device Boosts Bone Regeneration

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Scientists in Japan have developed a plasma device that promotes bone regeneration in fractures.

Unlike blood plasma, plasma here refers to the fourth state of matter, effectively a highly ionised gas, which has been long investigated as an effective surgical scalpel which cauterises tissue as it cuts. Other recent applications of plasma technology include surface sterilisation.

Now, a new type of plasma device, termed non-thermal atmospheric pressure plasma (NTAPP), was successfully tested in healing of bone fractures in animal bone defect models. It is cooler than most plasmas that are typically used. In a study published in PLOS ONE, researchers from Osaka City University detailed their findings using the technology in this world-first application.

Acceleration of cell growth
“NTAPP is considered a new therapeutic method,” said first author Akiyoshi Shimatani, “as it has been shown to accelerate cell growth when applied at low enough levels.” He explained that in an ambient atmosphere it can generate highly reactive oxygen and nitrogen species (RONS) which can be directly exposed to tissues.

Indirect treatments have shown the potential advantages of plasma in supporting the creation of stem cells that cause reactive oxygen species and in inducing osteogenic differentiation and bone formation, however, as the team points out there is no report on directly using NTAPP for bone fracture therapy. “Direct exposure of NTAPP is a key part of this study” states Jun-Seok Oh, professor at the OCU Graduate School of Engineering and advisor to the study, “It required a device specifically designed to generate and deliver RONS to areas of the bone defect ‘effectively’.”

The research group developed a pencil-like plasma device that can effectively generate and deliver RONS to an animal model with a well-established critical bone defect, allowing the team to search for the optimal exposure conditions. Comparing groups that were treated with NTAPP for 5, 10, and 15 minutes to control groups with no plasma administered, micro-CT images at eight weeks showed the 10-minute treatment time as the most successful bone regeneration with 1.51 times larger bone volume than the control group.

Since micro-CT images could not determine whether a bone defect has been filled with new bone, tissue or both, the team also ran a histological analysis and confirmed bone defects in the groups treated with plasma were in fact filled with new bone, and had no tissue or gaps like the control groups.

Precision therapy
The biological effect of plasma, like other therapies, depends on the treatment dose delivered into the targets. Although future research will be needed to clarify why the study saw the most bone regeneration during the 10-minute treatment period, surface wettability is understood to promote greater cell spreading and adhesion to biomaterials and implants. Hiroaki Nakamura, professor at the Graduate School of Medicine explained: “We wondered if something similar was occurring where we saw a strong generation of new bone. And we found that compared to the control group, bone surface of the plasma-treated group as statistically and significantly more hydrophilic.”

The research team hopes the plasma device they developed can be applied for surgical use.

Source: Osaka City University

Categories : Skeletal SystemTags :

Osteoclast Signalling Could Yield Osteoporosis Treatments

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A new discovery about a signalling function in osteoclasts suggests a potential treatment target for osteoporosis and for bone loss from rheumatoid arthritis.

The findings from University of Virginia School of Medicine researchers and their collaborators help us understand why osteoclasts begin to break down more bone than the body replaces.

“Bone degradation and subsequent repair are fine-tuned through complex interactions between the cells that degrade the bone – osteoclasts – and those that produce new bone matrix. Simple elimination of osteoclasts is, therefore, not always the best approach to treat pathologic bone loss. Instead, we found a ‘signalling node’ in osteoclasts that regulates their function in degrading the bone, but doesn’t reduce osteoclast numbers,” said researcher Sanja Arandjelovic of UVA’s Department of Medicine and UVA’s Carter Immunology Center.

With further research, it may be possible for scientists to one day be able to develop drugs that target the signalling node to prevent or treat bone loss. This discovery also helps explain why some previous attempts to develop osteoporosis treatments produced disappointing results.
Researcher Kodi Ravichandran, chair of UVA’s Department of Microbiology, Immunology and Cancer Biology and director of UVA’s Center for Cell Clearance, noted the potential of the findings to inform efforts to develop better treatments for osteoporosis: “In this study,” he said, “we identified previously unappreciated factors that contribute to osteoclast function that are truly exciting and open up new avenues to pursue.”

The researchers have found an important contributor, a cellular protein called ELMO1, which promotes the activity of the bone-removing osteoclasts. Osteoclasts are critical for bone health, as they normally remove just enough to stimulate new bone growth. The problem arises when the osteoclasts become too aggressive and remove more bone than the body makes, resulting in bone mass loss.

This excessive bone degradation is likely influenced by genetic factors, the researchers say. They note that many of the genes and proteins linked to ELMO1 have been previously associated with bone disorders and osteoclast function.

Encouragingly, the researchers were able to prevent bone loss in lab mice by blocking ELMO1, including in two different models of rheumatoid arthritis. That suggests clinicians may be able to target the protein in people as a way to treat or prevent bone loss caused by osteoporosis and rheumatoid arthritis, the researchers say.

They note that prior efforts to treat osteoporosis by targeting osteoclasts have had only mixed success, and they offer a potential explanation for why: Osteoclasts not only remove bone, but play a role in calling in other cells to do bone replacement. As such, targeting ELMO1 may offer a better option than simply waging war on the osteoclasts.

“We used a peptide to target ELMO1 activity and were able to inhibit degradation of the bone matrix in cultured osteoclasts without affecting their numbers,” Ravichandran said. “We hope that these new osteoclast regulators identified in our study can be developed into future treatments for conditions of excessive bone loss such as osteoporosis and arthritis.”

Source: University of Virginia