Molecular changes indicative of cartilage degeneration and osteoarthritis development in patients with anterior cruciate ligament injury Pathophysiology of musculoskeletal disorders

Abstract

Background: Anterior cruciate ligament (ACL) tear is considered a risk factor for osteoarthritis development. The purpose of our study was to investigate the expression levels of the apoptotic enzyme caspase 3, pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) and degrading enzyme matrix metalloproteinase 13 (MMP-13), all indicative of cartilage degeneration and osteoarthritis development in patients' chondrocytes after ACL rupture. Methods: We investigated the correlation between grade of cartilage degradation and time from injury or patients' age. IL-1β, IL-6 and MMP-13 mRNA expression levels were investigated in normal (n = 4) and chondrocytes from patients with ACL rupture (n = 33) using real-time polymerase chain reaction (PCR). Moreover, MMP-13 and caspase-3 protein expression levels were evaluated by western blot analysis. Trend analysis and correlation coefficient were performed to derive the relations between gene expression (MMP13, IL-6, IL-1β) and grading of cartilage defects and between gene expression (MMP13, IL-6, IL-1β) and patients' age, respectively. Results: Correlations were established between grade of cartilage degradation and time from injury. MMP-13, IL-6, IL-1β and caspase 3 expression levels were significantly upregulated in chondrocytes from ACL-deficient knee compared to normal. Among the patients with ACL-deficient knees, a significant upregulation of MMP-13 was observed in patients with ACL-rupture > 18 months from the time of injury to arthroscopy compared to patients with ACL-injury up to 18 months, whereas IL-6 and IL-1β expression was higher in chondrocytes from patients with more than 10 months ACL injury compared to those that underwent surgery within the first 10 months after injury. Νο association was observed between IL-1β, IL-6 and MMP-13 expression levels and cartilage defects or patients' age. Conclusion: Our results showed that increased levels of apoptotic, inflammatory and catabolic factors in chondrocytes are associated with time from injury and could contribute to cartilage degradation and osteoarthritis development after ACL rupture.