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Microarray analysis of healing rat Achilles tendon: Evidence for glutamate signalling mechanisms and embryonic gene expression in healing tendon tissue.

Molloy TJ, Wang Y, Horner A, Skerry TM, Murrell GA

Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Level 2 Research and Education Building, 4-10 South Street, Kogarah, Sydney, NSW 2217, Australia.

Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodelling. Though these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days post-injury, roughly representing the inflammation, proliferation, and remodelling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24h post-injury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signalling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterised as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing.

Published 15 August 2005 in J Orthop Res.
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