UCLA scientists create first roadmap of human skeletal muscle development

An interdisciplinary team of researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the University of California at Los Angeles (UCLA) has developed a first-of-its-kind roadmap of how human skeletal muscle develops, including the formation of muscle stem cells. The study, published in the peer-reviewed journal Cell Stem Cell, identified various cell types present in skeletal muscle tissues, from early embryonic development all the way to adulthood. Focusing on muscle progenitor cells, which contribute to muscle formation before birth, and muscle stem cells, which contribute to muscle formation after birth and to regeneration from injury throughout life, the group mapped out how the cells' gene networks – which genes are active and inactive – change as the cells mature. The roadmap is critical for researchers who aim to develop muscle stem cells in the lab that can be used in regenerative cell therapies for devastating muscle diseases, including muscular dystrophies, and sarcopenia, the age-related loss of muscle mass and strength. To create this roadmap, the researchers gathered highly specific data about two different groups of skeletal muscle cells: those from the human body, ranging from the fifth week of embryonic development to middle age, and those derived from human pluripotent stem cells the researchers generated in the lab. They then compared the genetic signatures of cells from both sources. The group found that pluripotent stem cell-derived muscle cells produced by all the methods they tried resembled muscle progenitor cells at an early developmental state and did not align to adult muscle stem cells. In addition to pinning down the true maturity of the lab-produced cells, this analysis also provided details about the other cell types present in skeletal muscle tissue across development and in populations derived from human pluripotent stem cells. These cells could play an essential role in muscle cell maturation and could be critical to improving methods to generate and support muscle stem cells in a dish.

Excess coffee consumption a culprit for poor health

Cappuccino, latte or short black, coffee is one of the most commonly consumed drinks in the world. But whether it's good or bad for your health can be clarified by genetics, as a world-first study from the University of South Australia's Australian Centre for Precision Health shows that excess coffee consumption can cause poor health. Using data from over 300,000 participants in the UK Biobank, researchers examined connections between genetically instrumented habitual coffee consumption and a full range of diseases, finding that too much coffee can increase the risk of osteoarthritis, arthropathy (joint disease) and obesity. In earlier research conducted by the research team, six cups of coffee a day were considered the upper limit of safe consumption. Reassuringly, the results suggest that, moderate coffee drinking is mostly safe. however it also showed that habitual coffee consumption increased the risks of three diseases: osteoarthritis, arthropathy and obesity. The researchers said the prevalence of these conditions in Australia and around the world shows how important it is to determine possible causes and influencers of the diseases. "For people with a family history of osteoarthritis or arthritis, or for those who are worried about developing these conditions, these results should act as a cautionary message,” the researchers said.

Arthritis clinical trial shows support for dextrose injection to alleviate knee pain

A randomized controlled trial conducted by a research team at a primary care clinic at the Chinese University of Hong Kong indicated that intra-articular-only injection therapy with hypertonic dextrose is safe and effective for alleviating symptoms of knee osteoarthritis. Over 52 weeks of treatment, the study, published in the Annals of Family Medicine, followed 76 patients who were between 45 and 75 years old who had been diagnosed with knee osteoarthritis and who suffered moderate to severe chronic knee pain for at least three months. One group of 38 patients received the hypertonic dextrose injection therapy, while the other had the same therapy only using normal saline. While both groups reported some improvement, the hypertonic dextrose group reported more significant reductions in pain by the conclusion of the study. The researchers note that longer-term follow-up, direct comparison with other injection therapies and cost-effective analysis are all needed.

Gene therapy in mice builds muscle, reduces fat

Exercise and physical therapy often are recommended to help people who have arthritis. Both can strengthen muscle, a benefit that also can reduce joint pain. But building muscle mass and strength can take many months and be difficult in the face of joint pain from osteoarthritis, particularly for older people who are overweight. A new study in mice at Washington University School of Medicine in St. Louis, however, suggests gene therapy one day may help those patients. The research shows that gene therapy helped build significant muscle mass quickly and reduced the severity of osteoarthritis in the mice, even though they didn't exercise more. The therapy also staved off obesity, even when the mice ate an extremely high-fat diet. The study was published online May 8, 2020, in the journal Science Advances. The research team gave eight-week-old mice a single injection each of a virus carrying a gene called follistatin. The gene works to block the activity of a protein in muscle that keeps muscle growth in check. This enabled the mice to gain significant muscle mass without exercising more than usual. Even without additional exercise, and while continuing to eat a high-fat diet, the muscle mass of these "super mice" more than doubled, and their strength nearly doubled, too. The mice also had less cartilage damage related to osteoarthritis, lower numbers of inflammatory cells and proteins in their joints, fewer metabolic problems, and healthier hearts and blood vessels than littermates that did not receive the gene therapy. The mice also were significantly less sensitive to pain. One worry was that some of the muscle growth prompted by the gene therapy might turn out to be harmful. The heart, for example, is a muscle, and a condition called cardiac hypertrophy, in which the heart's walls thicken, is not a good thing. But in these mice, heart function actually improved, as did cardiovascular health in general. Longer-term studies will be needed to determine the safety of this type of gene therapy. But, if safe, the strategy could be particularly beneficial for patients with conditions such as muscular dystrophy that make it difficult to build new muscle.

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