# Non-AGE collagen crosslinks

You have probably heard that sugar can stiffen collagen (those are AGE crosslinks). But there is a second, completely different kind your body makes on purpose. An enzyme called lysyl oxidase (LOX), plus its relatives (LOXL1 through 4), uses copper to convert specific lysine building blocks in fresh collagen and elastin into reactive aldehydes. Those then link up on their own to form strong covalent bridges: pyridinoline and deoxypyridinoline in collagen, desmosine and isodesmosine in elastin. This crosslinking is essential early on, since it gives your tissues their tensile strength. The trouble starts when it is overdone. Driven by signals like TGF-beta, low oxygen, and PDGF in fibrotic or tumor tissue, excess crosslinking makes tissue too stiff, scrambles how cells sense their surroundings, and helps tumors invade. The upside compared with AGE crosslinks: these LOX-made bonds can in principle be blocked with drugs such as beta-aminopropionitrile (BAPN), which makes this a separate drug target from the AGE/RAGE system.

## Sources

- Saito M, Marumo K. (2010). Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporosis International. https://doi.org/10.1007/s00198-009-1066-z
- Viguet-Carrin S, Garnero P, Delmas PD. (2005). The role of collagen in bone strength. Osteoporosis International. https://doi.org/10.1007/s00198-005-2035-9

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