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The Anti-Inflammatory Effects of Small Molecule Mediator (R)- PFI-2 in the Temporomandibular Joints of Rat and Mice Exposed to Common Inflammatory Mediators
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Introduction. TMD is a complex multi-factorial chronic inflammatory condition involving a host of life altering symptoms. The etiology of TMD is not well understood. To treat these chronic inflammatory conditions, small molecule mediators, such as (R)-PFI-2 have been selected to target robust protein kinase methyltransferases such as SETD7 in an effort to stop and even reverse the effects of chronic inflammation. Further study is needed to better understand its in vivo and in vitro potential. The aim of this investigation is to (1) establish a protocol for in-vitro and in-vivo (R)-PFI-2 concentrations that demonstrate anti-inflammatory effects in the TMJs of rats and mice and (2) show a predictable anti-inflammatory effect of (R)-PFI-2 both in-vitro and in-vivo in the TMJs of rats and mice. Material and Methods. A pilot study was completed to demonstrate predictable production of inflammation in the temporomandibular joints of rats and mice and establish an inflammatory/rescue protocol for future investigation. The in-vitro arm of this study used mice TMJs which were harvested, organ cultured and injected with IL-6 to demonstrate inflammation for both test groups, with only one test group receiving the rescue PFI-2 for comparison. Tissues were subjected to H/E analysis. Results. Rats: X-ray analysis demonstrated that the radio-opaque intertrabecular matter [proteoglycans or mineral formation] returned to the condylar bone following PFI-2 application. Micro-CT analysis demonstrated that inflammatory conditions resulted in an irregular rough, condylar surface. Following PFI-2 application, a partially rescued pathological TMJ phenotype could be observed. Histological staining demonstrated a connective tissue lining of the articular fossa and the condylar fibrous perichondrium that was fibrotic in inflammatory TMJs [CFA mice] and consisted of loose connective tissue in the healthy TMJs [control mice]. PFI-2 application resulted in a partial rescue. Immunohistochemistry demonstrated inflammatory conditions that resulted in an increased level of IL-1B expression and PFI-2 application that reduced the number of IL-1B positive cells. Mice: Histological slides demonstrated that PFI-2 restored bone and cartilage morphology and promoted muscle fiber growth. Conclusions. Our data suggest that PFI-2 may be useful as an anti-inflammatory mediator to reverse the effects of inflammatory TMD in rats and mice.
Briggs, Stephanie Renee (2019). The Anti-Inflammatory Effects of Small Molecule Mediator (R)- PFI-2 in the Temporomandibular Joints of Rat and Mice Exposed to Common Inflammatory Mediators. Master's thesis, Texas A & M University. Available electronically from