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Structured Abstract Objectives Investigate the expression and activity of inflammatory markers in response to different magnitudes of orthodontic forces and correlate this response with other molecular and cellular events during orthodontic tooth movement. Setting and Sample Population CTOR Laboratory; 245 Sprague Dawley male rats. Methods and Materials Control, sham, and 5 different experimental groups received different magnitudes of force on the right maxillary first molar using a coil spring. In the sham group, the spring was not activated. Control group did not receive any appliance. At days 1, 3, 7, 14, and 28, the maxillae were collected for RNA and protein analysis, immunohistochemistry, and micro‐CT. Results There was a linear relation between the force and the level of cytokine expression at lower magnitudes of force. Higher magnitudes of force did not increase the expression of cytokines. Activity of CCL2, CCL5, IL‐1, TNF‐α, RANKL, and number of osteoclasts reached a saturation point in response to higher magnitudes of force, with unchanged rate of tooth movement. Conclusion After a certain magnitude of force, there is a saturation in the biological response, and higher forces do not increase inflammatory markers, osteoclasts, nor the amount of tooth movement. Therefore, higher forces to accelerate the rate of tooth movement are not justified.

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