Research from the Perelman School of Medicine at the University of Pennsylvania shows that injury to connective tissue such as tendons can result in DNA damage that can impair healing.
Su-Jin Heo, an assistant professor at the Perelman School of Medicine, and colleagues believe this finding could help develop more effective therapies for hard-to-treat conditions such as tendinosis, which begins with a tendon injury but can be difficult to resolve.
“The research tells us, for the first time, that diseased connective tissue cells change the physical structure of their genomes and stop responding to normal physical cues from their environment,” said Heo, who was first author of the paper describing the work in Nature Biomedical Engineering.
“If we can figure out exactly why this happens, we might be able to ‘unlock’ the diseased state of these cells, and bring them back toward a healthy state.”
Heo and colleagues looked at how cells in diseased or damaged connective tissue respond to changes in their environment and how the spatial organization of chromatin, which makes up DNA, could be impacted.
They modeled this scenario in both tendon cells (tenocytes) and mesenchymal stromal cells, which act in a similar way to stem cells. When an environment that was similar to that of damaged or degenerating cells in the body was created through the presence of triggers such as altered oxygen tension and the presence of inflammatory markers, the cells began to re-order their chromatin. The researchers used super-resolution microscopy to visualize this.
The researchers believe these changes make it difficult for the damaged cells to heal properly without targeted therapies. “While we discovered that cells in diseased microenvironments lose their epigenetic memory, these results also suggest that epigenetic treatments—like small molecule medications—could restore healthy genome organization and may prove effective treatments in conditions affecting dense tissues,” said the study’s senior author, Melike Lakadamyali, an associate professor at the university, in a press statement. “That’s something that we plan to follow up on and test.”