Intra-articular Injection of Urinary Bladder Matrix Reduces Osteoarthritis Development

AAPS J. 2017 Jan;19(1):141-149. doi: 10.1208/s12248-016-9999-6. Epub 2016 Oct 24.

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.

Keywords: ACL transection; bioengineering; extracellular matrix; osteoarthritis; urinary bladder matrix.

MeSH terms

  • Animals
  • Anterior Cruciate Ligament Injuries / complications*
  • Disease Models, Animal
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Injections, Intra-Arterial
  • Male
  • Mice, Inbred C57BL
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / etiology
  • Osteoarthritis / immunology
  • Osteoarthritis / pathology
  • Tissue Extracts / administration & dosage
  • Tissue Extracts / therapeutic use*
  • Treatment Outcome
  • Urinary Bladder / chemistry*

Substances

  • Immunologic Factors
  • Tissue Extracts