Anti-Inflammatory Effects of Intra-Articular Hyaluronic Acid: A Systematic Review

Abstract

Objective Osteoarthritis (OA) is one of the leading causes of disability in the adult population. Common nonoperative treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroids, and intra-articular injections of hyaluronic acid (HA). HA is found intrinsically within the knee joint providing viscoelastic properties to the synovial fluid. HA therapy provides anti-inflammatory relief through a number of different pathways, including the suppression of pro-inflammatory cytokines and chemokines. Methods We conducted a systematic review to summarize the published literature on the anti-inflammatory properties of hyaluronic acid in osteoarthritis. Included articles were categorized based on the primary anti-inflammatory responses described within them, by the immediate cell surface receptor protein assessed within the article, or based on the primary theme of the article. Key findings aimed to describe the macromolecules and inflammatory-mediated responses associated with the cell transmembrane receptors. Results Forty-eight articles were included in this systematic review that focused on the general anti-inflammatory effects of HA in knee OA, mediated through receptor-binding relationships with cluster determinant 44 (CD44), toll-like receptor 2 (TLR-2) and 4 (TLR-4), intercellular adhesion molecule-1 (ICAM-1), and layilin (LAYN) cell surface receptors. Higher molecular weight HA (HMWHA) promotes anti-inflammatory responses, whereas short HA oligosaccharides produce inflammatory reactions. Conclusions Intra-articular HA is a viable therapeutic option in treating knee OA and suppressing inflammatory responses. HMWHA is effective in suppressing the key macromolecules that elicit the inflammatory response by short HA oligosaccharides.

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

“…These injections are hypothesized to provide lubrication, mild anti‐inflammatory effects, and pain relief. Meta‐analyses evaluating HA have shown variable responses, and there is increasing concern over a perceived lack of efficacy of some preparations (e.g., low‐molecular weight, non‐crosslinked) . If non‐surgical approaches are not successful, treatment options for advanced OA are limited to partial or total knee arthroplasty, while focal chondral defects can be treated with joint preserving options, including marrow stimulation with or without augmentation, osteochondral autografts and allografts, cell‐based therapy, scaffolds, osteotomy, and meniscal transplantation .…”

Human Urine-Derived Stem Cells: Potential for Cell-Based Therapy of Cartilage Defects

“…As reported by Venable et al [ 28 ], HA may be associated with cartilage damage in early pathologic changes of OA. The treatment of OA by intra-articular HA injection has been commonly used to promote cartilage repair, and the mechanisms contributing to this function are proposed to include the suppression of proinflammatory cytokines and chemokines, the promotion of the anabolism, and the relief of pain [ 29 , 30 ]. Nevertheless, the effects are controversial [ 31 – 33 ].…”

Study on the potential mechanism of anti‐inflammatory activity of covalently immobilized hyaluronan and heparin

“…Quite recently, it was also discovered that biomaterial‐induced inflammatory response can be attenuated by the use of glycosaminoglycans (GAG) like hyaluronic acid (HA) or heparin (Hep) that possess anti‐inflammatory properties (Wu et al, ; Zhang et al, ). For instance, the presence of intact GAG like hyaluronan (HA) is considered as a tissue integrity signal that reduces inflammation through its binding to CD44, a cell‐surface glycoprotein, which promotes the production of anti‐inflammatory cytokines (IL‐2 and IL‐10; Altman et al, ; Chen et al, ). In addition, this interaction causes a negative regulation of the pro‐inflammatory toll‐like‐receptor (TLR) signaling in which TLR is considered as an immunoreceptor mediator for NF‐кB activation (Avenoso et al, ).…”