Abstract
ObjectiveTo investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury.MethodsNon-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis.ResultsLoading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints.ConclusionWhile we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP.
Highlights
Osteoarthritis (OA) is a leading cause of disability worldwide
Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± platelet-rich plasma (PRP) or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints
Therapeutic efficacy of hyaluronan and PRP in a mouse knee injury model not necessarily represent the official views of the National Institutes of Health or the National Institute of Arthritis and Musculoskeletal and Skin Diseases
Summary
Osteoarthritis (OA) is a leading cause of disability worldwide. Post-traumatic OA (PTOA) in particular is a frequent cause of disability following trauma to the weight-bearing joints. Several invasive injury models such as injecting collagenase into the joint [2], using a needle to induce anterior cruciate ligament (ACL) transection in the closed knee, or using surgical techniques to transect or disrupt the ligaments or the medial meniscus of the knee [3, 4] have been widely used. These models do not mimic clinically relevant injury conditions due to invasive nature and non-physiologic injury methods. The wide spectrum of changes in the knee joint following tibial loading may be targets for treatment options
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