Biochemical identification and immunolocalizaton of aggrecan, ADAMTS5 and inter-alpha-trypsin-inhibitor in equine degenerative suspensory ligament desmitis.

This study examined the suspensory ligaments in horses with degenerative suspensory ligament desmitis (DSLD), looking in particular for proteins and enzymes associated with tissue inflammation and failure to heal. The researchers found significantly increased levels of certain components, suggesting that ligament degeneration in DSLD involves ongoing inflammatory response and stalled healing processes.

Research Context

• The study focuses on a condition in horses known as degenerative suspensory ligament desmitis (DSLD). This is a debilitating disorder that results in lameness due to degeneration of the ligaments.
• To better understand the progression of this condition, the team analyzed components within the suspensory ligaments of horses affected, compared to those of unaffected horses.
• The core elements examined were proteoglycans (molecules essential for connective tissue health), ADAMTS-aggrecanases (a specific group of enzymes that degrade proteoglycans), and inter-alpha-trypsin inhibitor (a protein complex related to inflammation and tissue repair).

Research Findings

• The analysis found that the suspensory ligaments of horses with DSLD contained approximately 15 times the amount of a proteoglycan called aggrecan, compared to the ligaments in normal horses.
• The aggrecan protein in the DSLD-affected ligaments was composed of two high molecular weight core protein species, one of which was found only in DSLD samples and seemed to match the aggrecan produced by equine mesenchymal stem cells. This suggests potential involvement of stem cells in the disease process.
• The DSLD-affected ligaments also showed high levels of the ADAMTS4 and ADAMTS5 enzymes, as well as an elevated concentration of the inter-alpha-trypsin inhibitor.
• The ADAMTS5 enzyme in the affected ligaments was primarily found as a large molecular weight complex, which was not the case in the normal ligaments. This finding suggests a possible role of this enzyme complex in the disease progression.

Research Implications

• The team concluded that ligament degeneration in DSLD appears to involve an inflammatory process characteristic of nonhealing wounds, possibly involving chondrogenic progenitor cells (stem cells that can develop into cartilage).
• The prominence of aggrecan in the disease suggests it plays a significant role in the incomplete healing processes. This is supported by the observation that accumulation of aggrecan is also a feature of the healing process in the absence of ADAMTS5, as seen in ADAMTS5 knockout mice.
• The authors propose that the disease process in DSLD involves tissue inflammation and the binding of ADAMTS5 into a larger molecular complex. This identification and understanding of specific biochemical changes in the degenerating ligaments provide further insight into the disease and may serve as a foundation for future therapeutic approaches.