Glucosamine and O-GlcNAcylation: a novel immunometabolic therapeutic target for OA and chronic, low-grade systemic inflammation?

Abstract

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Human Osteoclasts/Osteoblasts 3D Dynamic Co-Culture System to Study the Beneficial Effects of Glucosamine on Bone Microenvironment

“…It is worth mentioning that, in addition to the well-known role of its participation in the synthesis of components of the extracellular matrix [1,30], GlcN is the precursor of N-Acetyl-glucosamine which is added to serine and threonine residues of nuclear and cytoplasmic proteins in the O-GlcNAcylation posttranslational modi cation [31]. O-GlcNAcylation plays a critical role in the regulation of both cellular homeostasis, in response to nutritional or hormonal cues, but also in response to stress or damage [32]. A recent study reported that an increase of global O-GlcNAcglycosylation occurs during the early stages of osteoblast differentiation in MC3T3-E1 cells, but not during osteoclastic differentiation of RAW264 cell line [33].…”

Glucosamine sulphate: an umbrella review of health outcomes

“…65 Further studies are encouraged in order to confirm these promising findings, since in the UK Biobank the data are reported for different glucosamine preparations and not specifically for GS. Regarding the mechanisms of action that can justify these epidemiological findings, we can argue that GS may interfere with some pro-inflammatory pathways such as nuclear factor kappa-B, mitogenactivated protein kinase and phosphatidyl-inositol-3-kinase-dependent pathways 66,67 that are usually involved in the pathogenesis of diabetes. 68 Finally, our umbrella review is, in our opinion, important since GS use was associated with a similar incidence in adverse effects, compared with placebo, suggesting that its use is safe.…”

Response to: ‘Correspondence on “Glucosamine and O-GlcNAcylation: a novel immunometabolic therapeutic target for OA and chronic, low-grade systemic inflammation?’ by Angelides and Manolios

“…2 Our editorial made some hypothetical considerations about the mechanism of action of this compound. 3 The editorial also commented on the difficulty of detecting a beneficial effect of glucosamine in OA, due to the modesty of the therapeutic effect, as well as the weakness of the methodological tools employed in OA clinical trials. 3 In some way, the relationship between glucosamine and OA takes us fully into the pathophysiology that revolves around immunometabolic regulation, a driver that can account for tissue deterioration in various chronic diseases and still with many aspects to be elucidated.…”

“…3 The editorial also commented on the difficulty of detecting a beneficial effect of glucosamine in OA, due to the modesty of the therapeutic effect, as well as the weakness of the methodological tools employed in OA clinical trials. 3 In some way, the relationship between glucosamine and OA takes us fully into the pathophysiology that revolves around immunometabolic regulation, a driver that can account for tissue deterioration in various chronic diseases and still with many aspects to be elucidated. The hexosamine biosynthesis pathway (HBP), through which glucosamine can be metabolised in the cell, integrates the main cellular metabolic molecules, such as carbohydrates, amino acids, lipids and nucleotides, and regulates the inflammatory response through many mechanisms.…”

“…The hexosamine biosynthesis pathway (HBP), through which glucosamine can be metabolised in the cell, integrates the main cellular metabolic molecules, such as carbohydrates, amino acids, lipids and nucleotides, and regulates the inflammatory response through many mechanisms. 3 It is an example of what immune-metabolic integration means in diverse and varied circuits of the organism, an essential concept to decipher the pathogenesis of many human diseases. These integrating processes have been scarcely studied in OA, despite its association with obesity, low-grade systemic inflammation and cardiovascular disease.…”