Abstract
BackgroundKnee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature.MethodsWe conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment.ResultsChondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products.ConclusionsThe non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.
Highlights
Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population
We aim to summarize the mechanisms of action for IA-hyaluronic acid (HA) treatment of knee OA described in the current literature in order to determine the validity of the above mechanisms of action
There are multiple observed effects of IA-HA treatment that produce chondroprotection, many of which are results of HA binding to cluster of differentiation 44 (CD44)
Summary
Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. Osteoarthritis (OA) of the knee is most often a slowly progressive joint disorder, it is one of the leading causes of disability of the adult population [1]. As OA progresses, natural HA concentration and the distribution of HA within the joint shifts towards lower ranges of HA molecular weight, leading to a degradation of the mechanical/viscoelastic properties of the endogenous synovial fluid [2, 10, 11]. IA-HA administration has aimed to restore this decline in HA concentration and the average molecular weight distribution within the OA knee [9]
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