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Bone and Spine

The Aging Skeleton: New Insights into Bone Cell Changes with Age

Scientists and researchers around the globe are investigating a series of mysteries about what happens to our bones over time.

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As we age, our bodies undergo natural changes that affect not only our physical appearance but also our internal structures. The trillions of cells that make up our skeleton are no exception, as they too experience wear and tear over time. Recent research has shed new light on the mysteries surrounding skeletal cell aging, offering exciting possibilities for improved treatments for osteoporosis and age-related bone loss.

A team of scientists led by The University of Texas at Austin, in collaboration with Mayo Clinic and Cedars-Sinai Medical Center, has made a significant breakthrough in understanding how our bones age. They found that osteocytes, the master regulators of bone health, undergo dramatic structural and functional changes with age that impair their ability to keep our bones strong.

Aging and stress can induce cellular senescence in osteocytes, resulting in cytoskeletal and mechanical changes that weaken bone. Osteocytes sense mechanical forces and direct when to build or break down bone. However, when exposed to senescent cells – damaged cells that stop dividing but don’t die – osteocytes themselves begin to stiffen. This cytoskeletal stiffening and altered plasma membrane viscoelasticity undermine their ability to respond to mechanical signals, disrupting healthy bone remodeling and leading to bone fragility.

Imagine the cytoskeleton as the scaffolding inside a building. When this scaffolding becomes rigid and less flexible, the building can’t adapt to changes and stresses, leading to structural problems. Similarly, stiffened osteocytes can’t effectively regulate bone remodeling, contributing to bone loss.

Senescent cells release a toxic brew of molecules, called senescence-associated secretory phenotype (SASP), which triggers inflammation and damage in surrounding tissues. These cells have been linked to the development of cancer and many other chronic diseases.

The researchers approached the issue from a different perspective, focusing on cell mechanics. Combining genetic and mechanical approaches could lead to improved treatments for aging cells. They’re exploring how mechanical cues might help reverse or even selectively clear these aging cells, similar to physical therapy helping restore movement when our joints stiffen.

In the future, biomechanical markers could not only help identify senescent cells but also serve as precise targets for eliminating them, complementing or offering alternatives to current drug-based senolytic therapies. Improved knowledge about how bones age could improve treatments for osteoporosis, a condition that leads to weakened bones and an increased risk of fractures, affecting millions worldwide.

The team plans to expand their research by exploring the effects of different stressors on osteocytes and investigating potential therapeutic interventions. This project is led by Tilton in collaboration with Kirkland, along with other co-authors from various institutions.

Alternative Medicine

Breaking Barriers in Diabetic Wound Healing: A Revolutionary “Smart” Gel Accelerates Blood Flow and Restores Tissue Repair

A new gel-based treatment could change the way diabetic wounds heal. By combining tiny healing messengers called vesicles with a special hydrogel, scientists have created a dressing that restores blood flow and helps wounds close much faster. In tests, the treatment healed diabetic wounds far quicker than normal, while also encouraging the growth of new blood vessels. Researchers believe this innovation could one day help millions of people with slow-healing wounds caused by diabetes and possibly other conditions.

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Breaking Barriers in Diabetic Wound Healing: A Revolutionary “Smart” Gel Accelerates Blood Flow and Restores Tissue Repair

Chronic diabetic wounds, particularly diabetic foot ulcers, pose a significant burden for patients due to impaired blood vessel growth and subsequent tissue repair issues. A groundbreaking study has unveiled a novel approach by combining small extracellular vesicles (sEVs) loaded with miR-221-3p and a GelMA hydrogel to target thrombospondin-1 (TSP-1), a protein that suppresses angiogenesis. This innovative bioactive wound dressing not only accelerates healing but also promotes blood vessel formation, offering a promising new approach to treating one of the most challenging complications of diabetes.

The study explores a new method to stimulate angiogenesis and speed up the healing process by targeting TSP-1 with miR-221OE-sEVs encapsulated in GelMA. This engineered hydrogel has shown significant enhancement in wound healing and blood vessel formation in diabetic mice, offering hope for more effective treatments in the future.

Researchers discovered that high glucose conditions commonly found in diabetic wounds lead to increased levels of TSP-1 in endothelial cells, impairing their ability to proliferate and migrate – key processes for angiogenesis. By utilizing miR-221-3p, a microRNA that targets and downregulates TSP-1 expression, they restored endothelial cell function. The engineered miR-221OE-sEVs were encapsulated within a GelMA hydrogel, ensuring a controlled release at the wound site.

In animal trials, this composite dressing dramatically accelerated wound healing, with a notable increase in vascularization and a 90% wound closure rate within just 12 days, compared to slower healing in control groups. This breakthrough has significant implications for diabetic wound care, offering patients more efficient and lasting wound healing solutions.

As further research and clinical trials progress, the promise of combining miRNA-based therapies with biocompatible hydrogels could become a cornerstone in regenerative medicine, opening up possibilities beyond diabetic foot ulcers. The technology could be adapted for use in treating other chronic wounds, such as those caused by vascular diseases, or even in regenerating tissues like bone and cartilage.

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Bone and Spine

The Quiet Side Effect of Semaglutide: How Losing Muscle Can Affect Weight Loss Success

Semaglutide, a popular anti-obesity drug, may come with a hidden cost: significant muscle loss, especially in women and older adults. A small study found that up to 40% of weight loss from semaglutide comes from lean body mass. Alarmingly, those who consumed less protein saw even more muscle loss—potentially undermining improvements in blood sugar control.

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In recent years, the anti-obesity medication semaglutide has gained popularity for its ability to melt fat effectively. However, a small study presented at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, highlights a concerning side effect of this medication – the potential quiet stripping away of muscle strength, particularly among women and older adults.

Losing muscle mass, also known as lean mass, is a common issue associated with weight loss in adults with obesity. This can have negative consequences on metabolism and bone health. Muscle plays an essential role in controlling blood sugar levels after meals and keeping bones strong. Approximately 40% of the weight lost from taking semaglutide comes from lean mass, including muscle.

The researchers conducted a three-month study involving 40 adults with obesity, divided into two groups: those prescribed semaglutide and those following a diet and lifestyle program called Healthy Habits for Life (HHL). The results showed that participants who took semaglutide lost more weight than those in the HHL group. However, the percentage of weight loss attributed to lean mass was similar between the two groups.

Further analysis revealed that being older, female, or consuming less protein was linked to greater muscle loss among participants taking semaglutide. Moreover, losing more muscle was associated with less improvement in blood sugar control (HbA1c levels).

Study lead researcher Melanie Haines emphasized the importance of preserving muscle during weight loss with semaglutide to reduce insulin resistance and prevent frailty in people with obesity. She also highlighted that higher protein intake may help mitigate muscle loss in these patients.

In conclusion, while semaglutide is an effective medication for weight loss, it’s essential to be aware of its potential side effects, particularly among vulnerable populations like women and older adults. By understanding the importance of preserving muscle mass during weight loss and incorporating higher protein intake into their diet, individuals can maximize the benefits of this medication and achieve a healthier, more sustainable weight loss outcome.

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Bone and Spine

Unlocking New Insights into Bone Marrow: Scientists Develop Revolutionary Imaging Technique

A new bone marrow imaging technique could change treatment for cancer, autoimmune disease and musculoskeletal disorders.

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The Indiana University School of Medicine has made a groundbreaking discovery in the field of medical research. A team of scientists has developed a revolutionary new imaging technique that allows for the visualization of bone marrow in mouse models with unprecedented clarity and precision. This breakthrough could have far-reaching implications for the development of new treatments and therapies for conditions affecting bone marrow, such as cancers, autoimmune diseases, and musculoskeletal disorders.

The new method utilizes the multiplex imaging tool Phenocycler 2.0, which enables researchers to visualize a record number of cellular markers within intact bone marrow tissue from mice. This is a significant advancement over traditional methods like flow cytometry, which requires disrupting complex tissues to study and quantify cell populations, and standard fluorescence imaging, which is limited to detecting only three cellular markers at a time.

“We are thrilled to have made this breakthrough,” said Sonali Karnik, PhD, assistant research professor of orthopedic surgery at the IU School of Medicine and co-lead author of the study. “Bone marrow is a complex tissue that plays an essential role in blood and immune cell formation, and housing valuable stem cells. Our new imaging approach offers a unique tool for a variety of research applications.”
The IU Cooperative Center of Excellence in Hematology team successfully applied the Phenocycler 2.0 tool to mouse bone marrow, expanding its capabilities beyond organs like the spleen and kidney. This technique has the potential to revolutionize our understanding of diseases affecting bone marrow and enable researchers to develop more effective treatments.

“The use of mouse models is widespread in studying human diseases,” said Reuben Kapur, PhD, a co-senior author on the study and director of the IU School of Medicine’s Herman B Wells Center for Pediatric Research. “This technique offers a promising new method for investigating conditions like autoimmune diseases, leukemia, and other disorders involving bone marrow.”
The IU Innovation and Commercialization Office has filed a provisional patent for the new imaging methodology, and the team is now working to expand the marker panel to include additional features such as bone, nerves, muscle, and more immune and signaling cell types.

This research was supported by funding from the National Institutes of Health, and its findings were recently published in Leukemia. The development of this revolutionary imaging technique has the potential to transform our understanding of bone marrow and lead to breakthroughs in treating conditions affecting it.

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