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. 2019 Jan;10(1):43-52.
doi: 10.1177/1947603517749919. Epub 2018 Feb 11.

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

Roy Altman  1 , Asheesh Bedi  2 , Ajay Manjoo  3 , Faizan Niazi  4 , Peter Shaw  4 , Philip Mease  5   6
Affiliations

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

Roy Altman et al. Cartilage. 2019 Jan.

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.

Keywords: anti-inflammatory; hyaluronic acid; knee; osteoarthritis.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Roy Altman is a consultant for Ferring Pharmaceuticals, Inc. Asheesh Bedi and Ajay Manjoo have no conflicts of interest to disclose. Peter Shaw and Faizan Niazi are paid employees of Ferring Pharmaceuticals Inc. Philip Mease is a consultant for Genentech, has a research grant with Genentech, Merck and Zynerba, and is a speaker for Lilly, Merck, Sun, and Zynerba.

Figures

Figure 1.
Figure 1.
Summary of the pro-inflammatory and anti-inflammatory responses of hyaluronic acid. CD44 = cluster determinant 44; ECM = extracellular matrix; ERKs = extracellular signal-regulated kinases; FAK = focal adhesion kinase; HA = hyaluronic acid; HER2 = human epidermal growth factor receptor 2; HYAL = hyaluronidase; ICAM = intercellular adhesion molecule–1; ICM = intracellular matrix; IL = interleukin; IRAK = interleukin-1 receptor-associated kinase; MAPK = mitogen activated protein (MAP) kinase; MMP = matrix metalloproteinase; MyD88 = myeloid differentiation primary response 88, NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; NO = nitric oxide; PG = proteoglycan; PGE = prostaglandin E2; TAK1 = transforming growth factor-β (TGF-β)-activated kinase; TAL1 = T-cell acute lymphocytic leukemia protein 1; TIMP = tissue inhibitor of metalloproteinases; TLR = toll like receptor; TNF = tumor necrosis factor; TRAF6 = TNF receptor associated factors.
Figure 2.
Figure 2.
Literature Search.
See this image and copyright information in PMC

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