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Abstract
Introduction Degenerative changes in tendinopathy may be related to imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) [Jones, 2006]. The rate of human Achilles tendon rupture in women was noted to start to increase after menopause [Maffulli, 1999]. This study examines the effect of surgical menopause on rabbit patellar tendons (PTs) comparing molecular expression of MMPs and TIMPs. We hypothesised that PTs from rabbits following ovariohysterectomy (OVH) surgery would have increased MMP expression and decreased TIMP expression compared with PTs from intact normal rabbits.
Methods PTs from three groups of female New Zealand White rabbits were evaluated: intact normal (n = 8; 1-year-old), adult OVH (n = 8, 14 weeks post-OVH surgery at 1-year-old), adolescent OVH (n = 9, 33 weeks post-OVH surgery at 15-weeks-old). PTs underwent RT-qPCR with 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 Kruskal-Wallis tests with Conover post-hoc analyses.
Results The expression of TIMP-2 was decreased in PTs from adult OVH rabbits and adolescent OVH rabbits compared with PTs from intact normal rabbits (p < 0.05; Figure 1).
TIMP-2 mRNA levels in patellar tendons
The expression of TIMP-3 was decreased in PTs from adolescent OVH rabbits compared with PTs from intact normal rabbits (p < 0.05; Figure 2). TIMP-3 expression was decreased in PTs from adolescent OVH rabbits compared with adult OVH rabbits (p < 0.05; Figure 2). The expressions of MMP-1, MMP-3, MMP-13 and TIMP-1 were not statistically different when comparing PTs from the three groups.
TIMP-3 mRNA levels in patellar tendons
Discussion TIMP-2 expression in patellar tendon was decreased following surgical menopause in adult and adolescent rabbits and TIMP-3 expression in patellar tendon was decreased following surgical menopause in adolescent rabbits, with no changes in the other TIMPs and MMPs investigated. These findings suggest an MMP/TIMP expression imbalance towards degradation in tendon with loss of oestrogen. Although TIMP-2 and TIMP-3 expression were not changed in human degenerated patellar tendons [Parkinson, 2010] compared with normal tendons, TIMP-3 expression was decreased in human degenerated Achilles tendons [Jones, 2006] and TIMP-2 and TIMP-3 expression were decreased in human ruptured Achilles tendons [Jones, 2006] and human ruptured rotator cuff tendons [Lo, 2004] compared with normal tendons.
Acknowledgements NSERC, CIHR
References Jones et al. Arthritis Rheum. 2006;54:832–842
Maffulli et al. Clin J Sport Med. 1999;9:157–160
Parkinson et al. Arthritis Rheum. 2010;62:3028–3035
Lo et al. Am J Sports Med. 2004;32:1223–1229