The impact of forced joint exercise on lubricin biosynthesis from articular cartilage following ACL transection and intra-articular lubricin's effect in exercised joints following ACL transection

Abstract

Objective: To evaluate the impact of forced joint exercise following acute knee injury on lubricin metabolism and its relationship to cartilage degeneration and to assess chondroprotection of a single-dose purified human lubricin injection in exercised injured joints.

Methods: Anterior cruciate ligament transection (ACLT) was performed in rats with six experimental groups; 3-week post-ACLT, 3-week post-ACLT + exercise, 5-week post-ACLT, 5-week post-ACLT + exercise, and 5-week post-ACLT + exercise treated with intra-articular phosphate buffered saline (PBS) or lubricin. Joint exercise was achieved using a rotating cylinder at a speed of 6 rpm for 30 min daily, 5 days a week starting 1 week following surgery. Cartilage lubricin expression in injured joints was determined. Histological analyses included Safranin O/Fast Green, activated caspase-3, and lubricin mRNA in-situ hybridization. Assessment of cartilage damage was performed by osteoarthritis research society international (OARSI) modified Mankin scoring and urinary CTXII (uCTXII) levels.

Results: At 3 weeks, lubricin expression in exercised ACLT joints was significantly (P < 0.001) lower compared to ACLT joints. The OARSI scores were significantly (P < 0.001) higher in the ACLT + exercise animals compared to ACLT animals at 5 weeks. Compared to 3-week ACLT, 3-week ACLT + exercise cartilage showed increased caspase-3 staining. Compared to ACLT + exercise and PBS-treated ACLT + exercise, lubricin intra-articular treatment resulted in a significant increase (P < 0.001) in cartilage lubricin gene expression and a reduction (P < 0.05) in uCTXII levels.

Conclusion: Joint exercise resulted in decreased lubricin cartilage expression, increased cartilage degeneration and reduced superficial zone chondrocyte viability in the ACLT joint. Intra-articular lubricin administration ameliorated cartilage damage due to exercise and preserved superficial zone chondrocytes' viability.