Abstract
ObjectiveTo determine if temporomandibular joint chondrocyte apoptosis is induced in rats with dental biomechanical stimulation and what a role TNF takes.MethodsThirty-two rats were divided into 4 groups (n = 8/group) and exposed to incisor mal-occlusion induced by unilateral anterior crossbite biomechanical stimulation. Two groups were sampled at 2 or 4 weeks. The other two groups were treated with local injections of a TNF inhibitor or PBS into the temporomandibular joints area at 2 weeks and then sampled at 4 weeks. Twenty-four rats either served as unilateral anterior crossbite mock operation controls (n = 8/group) with sampling at 2 or 4 weeks or received a local injection of the TNF inhibitor at 2 weeks with sampling at 4 weeks. Chondrocytes were isolated from the temporomandibular joints of 6 additional rats and treated with TNF in vitro. Joint samples were assessed using Hematoxylin&eosin, Safranin O, TUNEL and immunohistochemistry staining, real-time PCR, fluorogenic activity assays and Western blot analyses. The isolated chondrocytes were also analyzed by flow cytometry.ResultsUnilateral anterior crossbite stimulation led to temporomandibular joint cartilage degradation, associated with an increase in TUNEL-positive chondrocytes number, caspase-9 expression levels, and the release of cytochrome c from mitochondria at 2 weeks without changes in TNF and caspase-8 levels until after 4 weeks. TNF stimulated apoptosis of the isolated chondrocytes and up-regulated caspase-8 expression, but did not change caspase-9 expression levels. Local injection of TNF inhibitor down-regulated caspase-8 expression and reduced TUNEL-positive cell number, but did not reverse cartilage thickness reduction, caspase-9 up-regulation or cytochrome c release.ConclusionsUnilateral anterior crossbite stimulation induces mitochondrion-mediated apoptosis of articular chondrocytes. TNF accelerated the unilateral anterior crossbite induced chondrocytes apoptosis via death-receptor pathway. However, anti-TNF therapy does not prevent cartilage loss in this model of temporomandibular joint.
Highlights
Biomechanical factors play important roles in several forms of osteoarthritis (OA), including temporomandibular joint disorder (TMD) [1]
Unilateral anterior crossbite stimulation led to temporomandibular joint cartilage degradation, associated with an increase in TUNEL-positive chondrocytes number, caspase-9 expression levels, and the release of cytochrome c from mitochondria at 2 weeks without changes in tumor necrosis factor (TNF) and caspase-8 levels until after 4 weeks
We enhanced this form of aberrant dental biomechanical stimulation, which we termed the unilateral anterior crossbite (UAC) model, by attaching metal tube crowns to the left incisor of rats
Summary
Biomechanical factors play important roles in several forms of osteoarthritis (OA), including temporomandibular joint disorder (TMD) [1]. Based on biomechanical principles [2], we created an abnormal dental occlusion, an experimentally created type of disordered occlusion that induces OA-like changes in the local cartilage of the temporomandibular joint (TMJ) [3,4,5,6,7] accompanied by an increase in articular chondrocyte apoptosis We enhanced this form of aberrant dental biomechanical stimulation, which we termed the unilateral anterior crossbite (UAC) model, by attaching metal tube crowns to the left incisor of rats. Caspase-9 is activated by mitochondrial pro-apoptotic signaling [16], whereas caspase-8 is activated during tumor necrosis factor (TNF) receptor-mediated apoptosis [17] It is not known if there is increased chondrocyte apoptosis in UAC-induced TMJ degradation or whether and what a role of TNF takes
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