Effect of distraction rates on expression of tissue inhibitors of matrix metalloproteinases in rabbit mandibular distraction osteogenesis

Abstract

Bone induction and ossification in distraction osteogenesis is related to the biological environment created by the mechanical tension. When compared with distraction at a normal rate, rapid distraction has demonstrated unreliable bone healing. Tissue inhibitors of matrix metalloproteinases (TIMPs) are nature inhibitors of matrix metalloproteinases (MMPs), which are capable of degrading bone matrix during the remodeling process. We hypothesize that different distraction rates may produce different TIMPs expression patterns, which will ultimately lead to different results in bone formation and remodeling. This study aims to compare the expression of endogenous TIMP-1 and -2 during rabbit mandibular distraction osteogenesis at normal and rapid rates. 27 New Zealand white rabbits were used. 24 rabbits were divided into 2 experimental groups with 12 rabbits in each group. Mandibular distraction was activated at 0.9mm/day lasting 12 days in the normal distraction group, and at 2.7 mm/day lasting 4 days in the rapid distraction group. 3 rabbits in each experimental group were sacrificed at day 1, week 1, week 2, and week 4 of consolidation. The other 3 rabbits without performing operation were used as control. Mandibular specimens were subjected for histological and Immunohistochemical assessment. The cells expressing TIMP-1 and -2 within the distraction regenerate were counted using a computer assisted image analyzing system. Histological study identified that normal rate distraction (0.9 mm/day) led to complete bone healing, whereas unreliable bone ossification was confirmed at rapid distraction (2.7 mm/day). The expression of TIMP-2 and -2 was localized in the osteoblasts, osteocytes and bone matrices of the trabeculae. Continuous up-regulation of TIMP-1 and -2 was observed in normal rate distraction group, whereas in the rapid lengthening model, TIMP-1 and -2 expression returned to a near-normal level at 4 weeks of consolidation. The change in the mechanical environment resulting from different rates of distraction leads to different expression of the TIMP-1 and -2 during mandibular distraction osteogenesis. The biological environment created by distraction at a normal rate is superior to the rapid distraction rate.