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Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo.


Maximus Peto’s Commentary

This group reports a remarkable association between plasma glucosepane and osteoarthritis, with as much as a 6-fold increase in advanced human osteoarthritis compared to controls. They also report some corroborating observations in guinea pig osteoarthritis. I wonder what glycation researchers make of *plasma* glucosepane being the compartment where glucosepane was assessed. If glucosepane is formed in collagen, how does it make it into plasma? Is it simply caused by normal tissue turnover? But if so, wouldn’t that mean that collagen-glucosepane could theoretically be turned over into plasma and removed or excreted from there? Maybe a kind of blood filtration/scrubber could be used to remove it?


Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo.
Arthritis Res Ther. 2018 Jun 22;20(1):131.
Legrand C, Ahmed U, Anwar A, Rajpoot K, Pasha S, Lambert C, Davidson RK, Clark IM, Thornalley PJ, Henrotin Y, Rabbani N
DOI: 10.1186/s13075-018-1636-6
PubMed publication date (edat): 6/23/2018

Abstract

BACKGROUND:
Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA.

METHODS:
Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids.

RESULTS:
Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52-0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009-0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003-0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. CONCLUSIONS: These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA. PMID: 29929535
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013878/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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