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Glucose enhances aggrecan expression in chondrocytes via the PKCα/p38-miR141-3p signaling pathway

PainSci » bibliography » Wu et al 2018

Two articles on PainSci cite Wu 2018: 1. The Complete Guide to Low Back Pain2. The Complete Guide to Patellofemoral Pain Syndrome

PainSci commentary on Wu 2018: ?This page is one of thousands in the bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.

This study shows that dextrose seems to be tasty stem cell food that encourages them to grow into big strong adult cartilage cells. And that does sound like a great idea in a worn out knee, which is why this study has been fairly widely cited by people interested in using dextrose prolotherapy for arthritis.

But they were testing animal stem cells. In petri dishes. And this is about as far from human clinical research as you can get. Their data is not useful for anything but (maybe) inspiring more research. Derp.

The authors did the research because they apparently already believe that prolotherapy works for osteoarthritis. What did they cite to support that belief? Just two papers: a ridiculous “garbage in, garbage out” review (Hauser et al) and a single tiny, weak, semi-controlled trial of prolotherapy for osteoarthritis (Topol). Not much to go on. 🙄

~ Paul Ingraham

original abstract Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

Aggrecan is a high molecular weight proteoglycan that plays a critical role in cartilage structure and the function of joints, providing intervertebral disc and cartilage with the ability to resist compressive loads. Aggrecan degradation in articular cartilage is a significant event in early-stage osteoarthritis (OA). Currently, no effective treatment exists for OA other than pain relief. Dextrose (D-glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the molecular mechanism of the glucose effect in OA and on the regulation of chondrogenesis. We show for the first time that glucose upregulates aggrecan expression and subsequent chondrogenesis in ATDC5 cells. Moreover, we found that glucose-induced aggrecan expression is mediated through the protein kinase Cα (PKCα)- and p38-dependent pathway. As demonstrated by microRNA (miR) and luciferase analyses, the glucose-induced PKCα/p38 signaling axis is responsible for downregulating miR141-3p which targets to the 3'untranslated region of aggrecan. In summary, we show that glucose enhances chondrogenesis by upregulating aggrecan expression via the PKCα-p38-miR141-3p signaling pathway. This result provides new insights into the mechanism of glucose on chondrogenesis.

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