Your horse’s body can’t function without tendons. These soft-tissue structures are essential for transmitting forces from muscles to bones to making them move during locomotion.
When a tendon injury occurs, that all-important tissue can tear. As if that isn’t bad enough, new research is showing that when those injuries occur to tendons covered by a synovial sheath, the inner tendon cells can be exposed to lubricating synovial fluid—a substance researchers recently determined is toxic for them.
Synovial fluid is in constant contact with tendons. But the tendon’s outer layer contains cells that are resistant to synovial fluid’s toxic nature. Once that outer layer is breached in certain types of injury, the cells on the inside of the tendon become exposed to the synovial fluid, which kills them, said Jayesh Dudhia, PhD, FHEA, a senior researcher in the Royal Veterinary College (RVC) Department of Clinical Sciences and Services, in Hertfordshire, UK.
This finding, that synovial fluid is toxic to inner tendon cells, could also help explain why injuries within tendon sheaths and bursae have a poor prognosis for healing and why stem cell therapy isn’t always successful, he said. What’s more, the tendon biology group at the RVC, headed by Dudhia and Roger Smith, PhD, DEO, FHEA, Dipl. ECVS, FRCVS, found that stem cells that attach to the tendon also tended to die when exposed to synovial fluid.
“There may be a number of reasons for this, but we strongly speculate that the tendon tissue exposed to the synovial fluid environment is not hospitable for stem cells to implant into the tendon and survive,” he said.
In their study, Dudhia and colleagues took superficial digital flexor tendons (SDFT) and deep digital flexor tendons (DDFT) from cadaver horses and cultured them in synovial fluid from the same or different horses. They cultured the outer synovial sheath cells separately from the inner tendon cells. Additionally, they cultured equine stem cells prepared from the bone marrow, alone, or implanted into SDFT and DDFT sections, in equine synovial fluid. Afterward, the scientists evaluated the cells’ viability through microscopic testing and analysis.
They found that inner tendon cells (the tenocytes) died rapidly when cultured with synovial fluid, Dudhia said. They noted that stem cells implanted into tendon sections and cultured with synovial fluid also did not survive. However, all these cells survived exposure to the synovial fluid when cultured alone. In short, the synovial fluid was toxic only when these cells were within the tendon tissue. They also found the same effect with human hamstring tendon.
This gives insight into the difficulties of healing injured tendons, Dudhia said, and raises questions about injecting stem cells into the injured tendons at these locations.
“A major function of the synovial fluid in the tendon sheath is as a lubricant to aid the smooth gliding of the tendon as it stretches and relaxes over a bony prominence during locomotion,” he said. “Its molecular composition, which is best as a lubricant, clearly is incompatible with the tendon cells once the outer protective layer is breached.”
An evolutionary mistake? It certainly seems like it.
“It’s an obvious conclusion to make, that evolution somehow did not get its act together when designing tendons that lie within the tendon sheath,” he said. “However, there are many examples of biological fluids that are toxic if they end up in the wrong place.” Digestive fluids, for example, can wreak havoc on internal tissues if they get past the thin digestive tract lining.
Evolution just didn’t “plan for” the kind of injuries modern horses face, Dudhia added.
“If evolution had pre-empted our, and horses’, overzealous exercising (a risk factor for injuries) of some tendons it would have redesigned the synovial fluid or made the tendon cells more resilient,” he said. “We need to learn more about the many components that make up the synovial fluid.”
While this research doesn’t yet provide concrete answers about how to improve tendon healing, it does lead toward the right direction.
“Approaches that can seal the injury from exposure to the synovial environment to encourage re-establishment of cells in the injury would appear to be the most worthwhile to consider,” he said.
It also opens the door for improving stem cell therapy, keeping in mind that the current injection method into the tendon synovial sheath creates too much toxic contact with synovial fluid.
“Alternatives to direct injection could include materials that act as scaffolds for the stem cells to adhere, and implanting such cell-loaded materials as this could conceivably protect the stem cells at least in the initial stages of repair,” Dudhia said. “It is a challenge but one that we are actively tackling.”
The study, “Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries,” was published in Connective Tissue Research.