Intraarticular induction of interleukin‐1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain

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Abstract
Objective To examine the effects of intraarticular induction of interleukin‐1β (IL‐1β) expression in adult mice. Methods We used somatic mosaic analysis in a novel transgenic mouse with an inducible IL‐1β transcription unit. Transgene activation was induced by Cre recombinase in the temporomandibular joints (TMJs) of adult transgenic mice (conditional knockin model). The effects of intraarticular IL‐1β induction were subsequently evaluated at the cellular, histopathologic, and behavioral levels. Results We developed transgenic mice capable of germline transmission of a dormant transcription unit consisting of the mature form of human IL‐1β as well as the reporter gene β‐galactosidase driven by the rat procollagen 1A1 promoter. Transgene activation by a feline immunodeficiency virus Cre vector resulted in histopathologic changes, including articular surface fibrillations, cartilage remodeling, and chondrocyte cloning. We also demonstrated up‐regulation of genes implicated in arthritis (cyclooxygenase 2, IL‐6, matrix metalloproteinase 9). There was a lack of inflammatory cells in these joints. Behavioral changes, including increased orofacial grooming and decreased resistance to mouth opening, were used as measures of nociception and joint dysfunction, respectively. The significant increase in expression of the pain‐related neurotransmitter calcitonin gene‐related peptide (CGRP) in the sensory ganglia as well as the auxiliary protein CGRP receptor component protein of the calcitonin‐like receptor in the brainstem further substantiated the induction of pain. Conclusion Induction of IL‐1β expression in the TMJs of adult mice led to pathologic development, dysfunction, and related pain in the joints. The somatic mosaic model presented herein may prove useful in the preclinical evaluation of existing and new treatments for the management of joint pathologic changes and pain, such as in osteoarthritis.

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