Fluoroquinolone Effects on Chondrocytes and Collagen

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A commenter on Floxiehope.com, “ImpossibleAdversity” left this comment that I thought made some valuable and informative connections:
There’s a rheumatologist/immunologist named Jonathan Edwards who occasionally posts on the web on researchgate and ME/CFS forums. He has views that would probably be considered “controversial” in his profession, but I’m not in a position to debate him on them.
 
Here’s something he posted regarding MMP enzymes in rheumatoid arthritis.
 
”For a long time it has been popular dogma that collagenases and other proteases degrade cartilage in inflammation in joints. However, if you think about it this does not make sense. Many patients with RA have inflammation in joints for months without any loss of cartilage. Even if the collagenase in the fluid was 98% inhibited the cartilage should be all gone after this time. Uninhibited collagenase will destroy cartilage in an hour or so. So the collagenase must be effectively 100% inhibited. Yet during some episodes of inflammation cartilage can be destroyed in a few days. The only solution to this problem I could find after thinking about it for decades was that type II collagen in live cartilage is totally protected, both from collagenase attack, and in fact from mechanical wear, by a constant extrusion of hyaluronan and small proteoglycans from its surface – much in the way that the skin of fish and dolphins constantly extrudes mucins to lubricate and provide a barrier against attack. However, if the chondrocytes die there will be no extrusion of macromolecules so the surface collagen will be directly available to attack. When I first became interested in joint pathology I looked at hundreds of slides of RA joints in the Path library at St Bart’s Hospital in London and one thing that struck me was that whenever there was cartilage invasion or resorption the underlying chondrocytes were dead (absent). So that made sense.”
 
If we apply this to fluoroquinolone toxicity it matches up:
”Human chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and 160 microg/ml) or Mg(2+)-free medium showed decreased ability to adhere to growth support, cell shape changes, and alterations in actin and vimentin cytoskeleton in a concentration dependent manner. Attachment of human chondrocytes to collagen type II coated cover slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on day 1. This effect even increased after 4 days of culture in the respective medium (32% in CFX and 58% in Mg(2+)-free group). We concluded that Mg(2+) deficiency is exerted via integrins, resulting in decreased ability to attach to extracellular matrix proteins and cytoskeletal changes.”
 
Ciprofloxacin starts killing away the chondrocytes, leaving the type II collagen vulnerable to attack by MMP enzymes, over just a few days.
 
Then we have the studies showing Cipro increases MMP expression:
https://www.ncbi.nlm.nih.gov/pubmed/12428247
https://www.ncbi.nlm.nih.gov/pubmed/20602464
 
Finally, we also know that Ibuprofen increases MMP expression:
https://www.ncbi.nlm.nih.gov/pubmed/19847888
 
I think Naproxen and glucocorticoids can also increase them but I don’t have the studies on hand.
 
So it’s a dual effect and basically a perfect storm.
The science behind fluoroquinolone adverse-reactions is really difficult to understand. But this community is doing a lot to make connections and lead researchers in the right direction. Thank you for the insight, “ImpossibleAdversity!”

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