Osteoclasts: The Biological Knife In Sutural Responses To Mechanical Stimulation

Abstract

Background: It is assumed that transverse force physically opens maxillary sutures and induces a tensile stress that directly stimulates bone formation. However, orthopedic/ orthodontic tensile stresses are static, which cannot directly stimulate bone formation. We hypothesize that the anabolic response to transverse force is indirect, resulting from inflammation-induced osteoclast activation followed by a transition into osteogenesis. The purpose of this study was to evaluate the tissue, cellular and molecular responses in the sutures during maxillary expansion. Materials & Methods: Adult Sprague-Dawley rats where divided into 4 groups: untreated Control (C), Sham (S), Experimental (Exp), and Experimental with nonsteroidal anti-inflammatory medication (Exp+NSAID). Maxillae were collected 0, 1, 3, 7, 14, and 28 days post-expansion for micro-computed tomography, fluorescence and light microscopy, gene and protein expression, and immunohistochemistry analysis. Results: The Exp group showed early expression of inflammatory cytokines in the mid-palatal suture that was followed by osteoclast activation, bone resorption and a transient decrease in bone density. A significant widening of the suture occurred only after osteoclast activation and bone resorption. Bone formation was delayed, occurring after the initial catabolic phase. NSAIDs significantly decreased the magnitude of maxillary sutural widening and bone formation in response to transverse forces. During the transition from the catabolic to the anabolic response, expression of communicator molecules between osteoclasts and osteoblasts increased significantly. Conclusion: We demonstrated that maxillary transverse force stimulated three distinct phases in the mid-palatal suture: 1) the Catabolic Phase starts with inflammatory markers and osteoclast recruitment and activity, 2) the Transition Phase, where osteoclasts activate osteoblast activity, 3) the Anabolic Phase, during which osteoblasts restore the integrity of the skeleton. INNOVATION: Our findings are novel and support a new theory for sutural response to orthopedic forces that emphasizes the importance of osteoclasts in the process and makes these cells the possible target of orthopedic treatment: 1) as the "biological knife" at the sutures that allows the separation of maxillae for orthopedic movement, and 2) as the trigger for osteoblasts activation and bone regeneration, anytime we need to stimulate bone formation especially at the surface of the cortical bone.