Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

Authors

Mitchell Knudsen, University of Nebraska Medical Center College of Dentistry
Matthew Bury, University of Nebraska Medical Center College of Dentistry
Callie Holwegner, Private Practice of Orthodontics, Cheyenne, WY, USA
Adam L. Reinhardt, Pediatric Rheumatology, Children’s Hospital, Omaha, NE
Fang Yuan, University of Nebraska Medical Center College of Pharmacy, Omaha, NE
Yijia Zhang, University of Nebraska Medical Center College of Pharmacy, Omaha, NE
Peter Giannini, University of Nebraska Medical Center College of Dentistry
D. B. Marx, University of Nebraska-LincolnFollow
Dong Wang, University of Nebraska-LincolnFollow
Richard A. Reinhardt, University of Nebraska Medical Center College of DentistryFollow

Document Type

Article

Date of this Version

2015

Citation

Knudsen et al. Arthritis Research & Therapy (2015) 17:267

DOI 10.1186/s13075-015-0772-5

Comments

© 2015 Knudsen et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

Abstract

Introduction: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.

Methods: Joint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations.

Results: CFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. 2; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm²).

Conclusions: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.