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.