Indian hedgehog: A mechanotranduction mediator in mandibular condylar cartilage

Abstract

AIM: Indian hedgehog (Ihh) acts as a critical mediator transducing mechanical signals to stimulate chondrocyte proliferation. The aims of this investigation were to clarify the cellular signal transduction pathway that senses and converts mechanical signals into tissue growth in the mandibular condyle, and evaluate the expression of Ihh and its relationship to the kinetics of replicating mesenchymal cells in condylar cartilage in natural growth and during anterior mandibular displacement. MATERIALS AND METHODS: Fifty female Sprague Dawley rats at 35 days of age were randomly divided into five control and experimental groups (n = 5). The experimental animals were fitted with functional appliances that continuously positioned the mandible 3.5 mm forward. Before sacrifice on days 3, 7, 14, 21 and 30, the rats were double labelled with two thymidine analogues in order to estimate the cell cycle of the replicating mesenchymal cells. The animals were first given an intraperitoneal injection of iododeoxyuridine (IdU) followed 1 hour later by another injection of bromodeoxyuidine (BrdU), and killed 1 hour after the last administration. The condyles were harvested and sections were obtained from the mid-sagittal plane. Immunohistochemical staining was carried out to discriminate the labelled cells with two specific antibodies. The temporal and spatial expression of Ihh was also evaluated by immunochemistry. RESULTS: Compared with natural growth, mandibular advancement led to a significant increase of replicating mesenchymal cell numbers for the first 14 days. The turnover time was shortened, without altering the S-phase of the cell cycle. Ihh was mainly localized in the proliferative and chondroblast layers, with a significantly higher expression in the proliferative layer on days 3 and 7 after mandibular advancement. CONCLUSION: Mandibular forward displacement promotes the amount and also the speed of the proliferation of mesenchymal cells. Ihh acts as a mediator of mechanotransduction in chondrogenetic cells in the condyle by converting mechanical signals to stimulate cellular proliferation.