Lubricin protects against cartilage degeneration following anterior cruciate ligament transection in rats

Despite the growing prevalence of post-traumatic osteoarthritis (OA), early and effective treatment options to delay surgical intervention remain limited. Lubricin is a naturally occurring glycoprotein produced by articular chondrocytes and synovial fibroblasts that functions as the principal boundary lubricant in joints. Recently, a recombinant lubricin-like glycoprotein (rhLub) with codon optimized mucin domain was reported to have a sustained residence time (> 6 weeks) following injection into the knee joint of healthy rats. To evaluate outcomes of rhLub injection, skeletally mature Sprague-Dawley rats of both sexes (n = 18) underwent bilateral anterior cruciate ligament transection (ACLT) to initiate post-traumatic OA, followed by three intra-articular injections of 25 µL of rhLub (1.3 mg/mL) or phosphate-buffered saline (PBS) at weekly intervals beginning 1 week post-operatively. Pain sensitization was evaluated weekly throughout the 12-week study with weightbearing and pressure application measurement (PAM). Frontal plane histologic sections of the medial femorotibial joint compartment were scored using Osteoarthritis Research Society International criteria. Injections of rhLub were well-tolerated. rhLub injections protected against cartilage degeneration and improved histologic scores in male rats. Mechanical hyperalgesia and cartilage degeneration scores were greater in female rats compared to males, irrespective of treatment. This study suggests that intra-articular rhLub therapy may be most efficacious in mild-to-moderate disease.