Humans have a salamander-like ability to regrow cartilage in joints, a team of scientists has found. Salamanders are well-known for being able to regrow new limbs, but it turns out that a similar process takes place in the human body, according to a study published in the journal Science Advances. The scientists from Duke Health identified a mechanism for cartilage repair which they say could have important implications, potentially opening the door to new treatments for osteoarthritis—the world's most common joint disorder—as well as methods to grow human body parts. "We believe that an understanding of this 'salamander-like' regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs," Virginia Byers Kraus, a senior author of the study from the departments of Medicine, Pathology and Orthopedic Surgery at Duke, said in a statement. For the research, the scientists used a technique known as "mass spectrometry" to determine the age of cartilage throughout the body. This analysis revealed that cartilage has different "ages" depending on where it is located: young in the ankles, middle-aged in the knees and old in the hips. "In our efforts to understand the proteins in cartilage, we discovered big differences in the chemical modifications of the proteins in hip, knee and ankle cartilages," Kraus told Newsweek. "These types of modifications build up if the tissue is not repairing or turning over—the process of getting rid of old protein while making new protein." "Hip cartilage proteins had an abundance of chemical modifications of proteins while the knee had moderate amounts and the ankle very few proteins with these chemical modifications," she said. "This showed that the ankle was in a high state of repair or turnover, the hip in a low state of repair and the knee in between." These results mimic those seen in animals which regenerate their limbs beginning at the furthest tips. "In searching for an explanation for these different levels of repair ability, we considered the possibility of salamander limb regeneration because their limbs regenerate best at the ends—the hands and feet," Kraus said. They also found that humans make use of some of the same molecules—called microRNA—that are key to limb regeneration in salamanders and other animals which can regrow body parts, such as zebrafish, African fresh water fish and other lizards. "In human cartilage, these [molecules] were present at a high level in human ankle cartilages, intermediate in knees and low in hips and strongly related to the 'age'—amount of chemical modifications—of proteins at the three joint sites," Kraus said. "Our results suggest that the principles underlying limb regeneration in limb regenerating animals involving regenerative microRNA, appear to be a biologic principle underlying the natural repair capability of human cartilage. To our knowledge, this is the first insight that human cartilage repair is linked to processes used in limb regeneration," she said. According to the researchers, the results could provide an explanation for why ankle injuries tend to heal quicker than knee and hip injuries, and why the latter two develop into arthritis less frequently. The study has significant implications, the team say, because it broadens our understanding of the microRNAs—which could be developed into medicines to treat or even reverse arthritis. "The traditional view has been that cartilage lining the joints throughout the body is all the same and does not repair or regenerate," Kraus said. "This research shows that cartilage at different sites is different and that cartilage has has a natural repair capacity that varies by joint site." "The implications are far-reaching, suggesting new treatments based on boosting, with regenerative microRNA, the natural human ability to repair cartilage," she said. "We think of it as "boosting our inner salamander capacity". We wonder, might it be possible to someday regenerate a human limb based on a deeper knowledge of how humans and salamanders are alike and unalike." Source
