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

Abstract

Objective. To examine the effects of intraarticular induction of interleukin-1␤ (IL-1␤) expression in adult mice.Methods. We used somatic mosaic analysis in a novel transgenic mouse with an inducible IL-1␤ 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-1␤ induction were subsequently evaluated at the cellular, histopathologic, and behavioral levels. Osteoarthritis (OA) manifests as a slowly progressing debilitating disease that affects one or more joints of the body. Clinical symptoms include pain, dysfunction, and swelling and enlargement of the joints. The primary pathologic features of OA are fibrillation and loss of articular cartilage, accompanied by remodeling of subchondral bone. OA seems to be a node of convergence for a number of potentially independent pathologic processes that, ultimately, can lead to joint dysfunction and pain (1). Although the role of inflammation in OA has been long debated (2), recent evidence now confirms proinflammatory cytokines as mediators in this disease (3). For example, the catabolism of OA cartilage is thought to involve the action of proinflammatory cytokines such as interleukin-1 (IL-1)

Amelioration of pain and histopathologic joint abnormalities in the Col1‐IL‐1βXAT mouse model of arthritis by intraarticular induction of μ‐opioid receptor into the temporomandibular joint

“…We injected 50 l of aqueous solution containing a total of 1 ϫ 10 6 infectious particles of FIV(HuMOR) ( Figure 1A) bilaterally into the TMJs of young adult Col1-IL1-␤ XAT -transgenic mice. A week later, these mice received an injection of solution containing a total of 5 ϫ 10 6 infectious particles of FIV(Cre) into each TMJ to induce transgene activation and arthritis, as previously described (35). HuMOR expression in the trigeminal ganglia was evaluated 8 weeks later by immunohistochemistry.…”

“…Grooming behavior was evaluated by adapting a method previously described (35). Briefly, mice were placed in a custom-made cage (12 ϫ 12 ϫ 12 inches) with 4 mirrored walls.…”

“…The brainstem and ganglia were cut frozen on a cryostat into 18-m-thick sections and collected on glass slides. Overall TMJ histopathologic findings were evaluated in Alcian blueorange G-stained sections, using a scale previously described by Wilhelmi and Faust (38) and used by Lai et al (35). Findings were scored on a scale of 0-4, where 0 ϭ no apparent changes, 1 ϭ superficial fibrillation or striation of cartilage, 2 ϭ injuries limited to uncalcified cartilage, 3 ϭ defects extending into calcified cartilage, and 4 ϭ deep defects extending into calcified cartilage.…”

“…GFAP immunoreactivity was measured in the brainstem and ganglion sections as the number of immunoreactive pixels in each microscopic field (10ϫ magnification), using image analysis software (NIH Image, National Institutes of Health, Bethesda, MD; online at: http://rsb.info.nih.gov/nih-image/) (35). The numbers of c-Fosϩ and IL-1␤ϩ cells in each microscopic field were counted by one investigator (SK).…”

“…XAT -transgenic mouse model of arthritis (35), in which adult mice develop pain, joint dysfunction, and osteoarthritis (OA).…”