Abstract
PurposeIntraarticular (IA) hyaluronic acid (HA) injection is used to reduce pain and improve mobility in knee osteoarthritis (OA). Little is known about histopathological changes underlying HA efficacy. This study investigated dose-related effects of 1% sodium hyaluronate (BioHA) on knee joint histopathology and pain responses in a medial meniscal tear (MMT) rat model of OA.MethodsFollowing MMT surgery, rats were randomized into treatment groups: single IA injection of vehicle, BioHA, or an avian-derived hyaluronic acid (hylan G-F 20) on Day 7; or 3 weekly injections of vehicle or BioHA on Days 7, 14, and 21. On Day 35, joints were evaluated by microscopic histopathology for cartilage degeneration, collagen degeneration, synovitis, and cytokine expression (tumor necrosis factor α, transforming growth factor β).ResultsJoint pathology for control animals was consistent with that expected for the MMT model. Rats treated with 3 injections of IA-BioHA had significantly reduced collagen degeneration (21%) relative to control animals. No significant change in collagen degeneration was observed for rats given a single injection of hylan G-F 20 or IA-BioHA compared to control animals. HA treatment did not affect cytokine expression.ConclusionsIA-BioHA viscosupplementation in a rat MMT model of OA showed preservation of joint cartilage and collagen. This effect was most pronounced on tibial surfaces having less severe injury, suggesting that treatment should be initiated early in the disease process. A comparison of responses to IA-BioHA or hylan G-F 20 in the MMT rat OA model suggest IA-BioHA may be more effective in preserving joint connective tissue.
Highlights
Osteoarthritis (OA) is characterized by synovitis, breakdown of articular cartilage, and changes in the quantity and quality of synovial fluid [16, 18]
To further investigate the potential benefits of Intra-articular injection of biologically derived hyaluronic acid (IABioHA) viscosupplementation on OA joint structure and to support future Hyaluronic acid (HA) formulation development, we investigated the dose-related effects of IA-BioHA on knee joint cartilage, collagen, synovitis, inflammatory cytokine expression, and pain responses in a well-characterized medial meniscal tear (MMT) rat model of OA [11]
The animals did exhibit mild changes in gait, consistent with what is expected after MMT surgery in the rat [14, 15]
Summary
Osteoarthritis (OA) is characterized by synovitis, breakdown of articular cartilage, and changes in the quantity and quality of synovial fluid [16, 18]. This study reported a significantly higher incidence of post-injection effusions in the hylan G-F 20 group vs the IA-BioHA group. Consistent with the latter observation are reports that crosslinked, high molecular weight, avian-derived HA may elicit acute local reactions after intra-articular injection [8, 10, 23]. Broad based analyses of clinical trials evaluating the effects of IA-HA in knee OA found higher molecular weight IA-HA products and those derived from bacterial fermentation are associated with superior efficacy and safety [1, 6]
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