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AGING UNIQUELY INFLUENCES TISSUE INHIBITOR OF METALLOPROTEINASE-2 (TIMP-2) EXPRESSION IN NORMAL TENDON
  1. G M Thornton,
  2. C R Reno,
  3. I K Y Lo,
  4. D A Hart
  1. McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada

    Abstract

    Introduction The incidence of tendinopathy increases with aging. Alterations to the balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) may play a role in the degenerative changes seen in tendinopathy.1 In addition, aging may have an effect on the expression of these molecules in tendon, as was found in skin.2 Our purpose in this study was to examine the effect of aging on patellar tendons from 1-year-old and 3-year-old rabbits comparing molecular expression of MMPs and TIMPs. Our hypothesis was that patellar tendons from 3-year-old rabbits would have increased MMP expression and decreased TIMP expression compared to patellar tendons from 1-year-old rabbits.

    Methods Patellar tendons from 1-year-old (n=8) and 3-year-old (n=6) female New Zealand White rabbits underwent RT-qPCR using rabbit specific primers for MMPs (MMP-1, MMP-3, MMP-13) and TIMPs (TIMP-1, TIMP-2, TIMP-3), and the housekeeping gene 18S. Data were compared using Mann Whitney U tests.

    Results Comparing patellar tendons from 3-year-old to 1-year-old rabbits, the expression of MMP-1, MMP-3 and MMP-13 did not change with aging. The expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02; figure 1). TIMP-1 and TIMP-3 expression were not affected by aging.

    Figure 1.

    MMP and TIMP Expression in Patellar Tendons from 1-year-old and 3-year-old rabbits. Expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02).

    Discussion Aging significantly decreased TIMP-2 expression in patellar tendon with no changes in the other TIMPs and MMPs investigated. This suggests a change in the balance of MMP/TIMP expression towards degradation in tendon with aging, or a significant shift in the MMP-independent activities of TIMP-2.3 In human skin, TIMP-2 expression was decreased with aging.2 Despite no change in TIMP-2 expression in degenerated human patellar4 and Achilles1 tendons compared to normal tendons, TIMP-2 expression was decreased in ruptured human Achilles1 and rotator cuff5 tendons compared to normal tendons.

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