Intra-articular injection of urinary bladder matrix reduces the development of post traumatic osteoarthritis

Abstract

Purpose: Urinary bladder matrix (UBM) is a naturally derived biomaterial derived from a cellular epithelial basement membrane and lamina propria of the porcine urinary bladder. The objective of this study was to assess the disease modifying ability of UBM in a mouse model of post traumatic osteoarthritis (OA). Methods: C57BL6 male mice underwent anterior cruciate ligament transection (ACLT) to induce OA. Two weeks after ACLT, 10 μl of UBM (ACell, Inc.) or saline was injected intra-articularly into the mouse joint. Cartilage integrity was assessed using OARSI scoring of histology at 4 and 8 weeks post ACLT and correlated with functional pain testing. Additionally, joints were harvested for quantitative PCR (qPCR) of cartilage and inflammatory markers at 4 and 8 weeks post ACLT. Results: In UBM treated animals, the average OARSI score was reduced from 3.28 (saline control) to 1.43 at 4 weeks, and to 1.92 at 8 weeks (p < 0.05), with more intense proteoglycan staining and intact articular cartilage. qPCR analysis was performed and fold changes calculated with respect to un-operated, age matched controls. This revealed that, compared to saline controls, UBM injected animals expressed significantly higher levels of the structural cartilage gene collagen 2α1 (on average 13.27 fold compared to 4.14 fold), aggrecan (9.24 fold compared to 3.99 fold), and the anti-inflammatory genes IL-4 (2.64 fold compared to 1.19 fold) and IL-10 (5.00 fold compared to 1.22 fold). These results correlated with the functional tests, in which the mice displayed a significant reduction of pain on the hot plate and incapacitance tester. Conclusions: UBM lessens cartilage degeneration in the ACLT model of OA. This therapeutic effect maybe due to the reduced inflammation in the joint and maintenance of high expression levels of proteoglycans, which may be helping to retain normal cartilage.