Abstract
Micronized porcine urinary bladder matrix (UBM) is an extracellular matrix biomaterial that has immunomodulatory and pro-regenerative properties. The objective of this study was to assess the ability of UBM to alter disease progression in a mouse model of post-traumatic osteoarthritis (OA). Ten-week-old wild-type C57BL/6 male mice underwent anterior cruciate ligament transection (ACLT) to induce OA. Two weeks after ACLT, UBM (50 mg/mL) or saline was injected into the mouse joint. At 4 and 8 weeks post-ACLT, cartilage integrity was assessed using OARSI scoring of histology, pain was evaluated, and joints were harvested for quantitative RT-PCR analysis of cartilage-specific and inflammatory gene expression. UBM-treated animals showed improved cartilage integrity at 4 and 8 weeks and reduced pain at 4 weeks compared to saline-injected mice. Animals injected with UBM expressed higher levels of genes encoding structural cartilage proteins, such as collagen2α1 and aggrecan, as well as anti-inflammatory cytokines, including interleukins 10 and 4. UBM decreased cartilage degeneration in the murine ACLT model of OA, which may be due to reduced inflammation in the joint and maintenance of high expression levels of proteoglycans.
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Acknowledgments
The authors would like to thank M. Frisk for editing, Okhee Jeon for histology scoring, The Wilmer NEI-NIH funded Imaging Core, the Wilmer Pooled Professor Fund, and Rhonda Grebe for confocal expertise. ACell Inc. for supplying UBM and providing financial support for the study through a Sponsored Research Agreement was also acknowledged.
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Guest Editor: Aliasger K. Salem
The original version of this article was revised: The original article had one of the authors incorrectly listed as “Matthew Wolf” instead of “Matthew T. Wolf”.
An erratum to this article is available at http://dx.doi.org/10.1208/s12248-016-0012-1.
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Fig. S1
UBM can reduce chondrocyte toxicity in the presence of IL-1 β. Alamar Blue cell toxicity test. Primary human chondrocytes were cultured in 10 ng/mL IL-1β and each experimental condition for 24 h before performing the Alamar Blue assay. Absorbance values were taken at 570 and 600 nm 3 h after addition of Alamar Blue and percent reduction of Alamar Blue was calculated based on control cells. (GIF 265 kb)
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Jacobs, H.N., Rathod, S., Wolf, M.T. et al. Intra-articular Injection of Urinary Bladder Matrix Reduces Osteoarthritis Development. AAPS J 19, 141–149 (2017). https://doi.org/10.1208/s12248-016-9999-6
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DOI: https://doi.org/10.1208/s12248-016-9999-6