The Nature of Tendon IInflammation

The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site) and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM) overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV) chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM.

From press release:

Scientists have discovered how tendons -- the fibrous tissue that connects muscle to bone -- become damaged through injury or the aging process in what could lead to new treatments for people with tendon problems.

The University of Manchester team, working with colleagues at Glasgow University, have been investigating 'adhesions', which are a build up of unwanted fibrous tissue on internal organs that have been damaged as a result of surgery or injury.

Adhesions cause organs to stick together and are extremely painful and distressing for patients, who often have to undergo surgery and rehabilitation. The estimated cost of adhesions to the NHS is £100 million each year.

In this study, published in the journal PLoS ONE, the researchers wanted to understand how tendon adhesions form, so examined the surface of healthy tendons and discovered that they are covered by a thin layer of skin.

"Tendons attach our muscles to bone and are essential for movement," said lead researcher Professor Karl Kadler, from the Wellcome Trust Centre for Cell Matrix Research in Manchester's Faculty of Life Sciences.

"In order to do this, tendons need to glide freely but when an adhesion forms the tendon can no longer travel over the bone, which causes pain, stiffness and reduced movement.

"We reasoned that the surface of tendons must contain a special cell that stops adhesions from forming in healthy people. We discovered that the tendon is actually covered by a thin layer of epithelial cells, which are usually found in skin.

"Undamaged tendons do not form adhesions but when the tendon 'skin' is damaged, the cells inside the tendon form an unwanted adhesion which begins to stick to nearby tissues."

The team were able to show that mice with defective cells at the surface of their tendons appeared to have difficulty walking and spontaneously develop tendon adhesions, even without surgery or injury.

Dr Susan Taylor, from The University of Manchester and co-author on the paper, added: "This study of tendon adhesions shows that the integrity of the surface of a tissue is critical in preventing adhesions. Furthermore, the discovery of this completely new layer of tendon cells changes the way we are thinking about how tendons are made during embryonic development and maintained in adulthood. Future research is aimed at finding ways of protecting the tendon epithelium in older people and in athletes."