Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health

Abstract

Osteoarthritis (OA) is a common form of arthritis in humans. It has long been regarded as a non-inflammatory disease, but a degree of inflammation is now recognized as being a vital inducer of subpopulation of OA. Besides inflammation, the establishment and development of OA are associated with alterations in metabolism and profiles of amino acids (AA), including glutamate- and arginine-family AA as well as their related metabolites (e.g., creatinine, hydroxyproline, γ-aminobutyrate, dimethylarginines and homoarginine). Functional AA (e.g., glutamine, arginine, glutamate, glycine, proline, and tryptophan) have various benefits (i.e., anti-inflammation and anti-oxidation) in treatment of inflammation-associated diseases, including OA. Thus, these AA have potential as immunomodulatory nutrients for patients with inflammation-induced OA.

T Cells in Osteoarthritis: Alterations and Beyond

“…The metabolism and transportation of amino acids also have a remarkable influence on T-cell activation and differentiation, especially for Th1 and Th17 cells, suggesting that amino acid metabolism also affects the pathogenesis of OA. Indeed, the establishment and development of OA are associated with alterations in the metabolism and profile of amino acids such as those of the glutamate and arginine families, as well as their related metabolites (e.g., creatinine, hydroxyproline, γ-aminobutyrate, dimethylarginines, and homoarginine) (4). Furthermore, intestinal microbiota have vital roles in T-cell responses, especially those of Th17 cells (102, 103), indicating the critical functions of intestinal microbiota in the pathogenesis of OA.…”

“…Recent compelling investigations have attributed the onset of OA to various person-level factors such as age, sex, obesity, and diet and joint-level factors such as injury, malalignment, and abnormal joint loading (3–5). Although more and more researchers have recently presented hypotheses concerning the involvement of these factors in OA, especially for person-level factors, few of their hypotheses have been demonstrated experimentally, and some have even been challenged by the latest observational studies and clinical trials (4, 6, 7). …”

“…The scientific community once understood OA to be induced by mechanical stress in the form of cartilage destruction, with minimal if any involvement of immune responses. Thus, OA was regarded as a non-inflammatory disease, in contrast with rheumatoid arthritis (RA), an inflammatory disease (4, 7, 12, 13). However, recent studies suggest that at least in certain patients, OA is an inflammatory disease; patients have frequently been found to exhibit inflammatory infiltration of synovial membranes (9–11).…”

Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study

“…Glutamine can be obtained from the diet or synthesized in the body from glutamate and a nitrogen donor and is the most abundant amino acid in the human blood. As a known regulator of a number of signaling pathways, glutamine is a potent anti‐oxidative agent with potential function in a number of inflammatory diseases, including OA . BCAAs, which cannot be endogenously synthesized, are essential amino acids, which are thought to play roles in a number of diseases including obesity and diabetes .…”

Diet-Intestinal Microbiota Axis in Osteoarthritis: A Possible Role

“…Several dietary factors have been reported to be involved in pathogenesis of OA, such as vitamins [26], amino acids [5], and magnesium [27]. However, further studies are needed to better define the association between OA and these dietary factors and to better understand the underlying mechanism for these dietary factors to regulate OA.…”