Effects of fluoroquinolone antibiotics on extracellular matrix-related phenotypes in tendon cells

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Fluoroquinolones (FQs) are broad-spectrum antibiotics with excellent absorption and tissue penetration.
• FQs can cause rare but serious collagen-associated adverse reactions, such as tendinopathy.
• The specific cellular mechanisms underlying FQ-induced tendinopathy, particularly changes in tenocyte extracellular matrix (ECM), are not well understood.

Purpose of the Study:

• To investigate the effects of fluoroquinolones on tenocyte-produced extracellular matrix (ECM) and related molecules.
• To elucidate the cellular phenotypes associated with fluoroquinolone-induced tendinopathy.

Main Methods:

• In vitro study using mouse tendon cells.
• Analysis of intracellular uptake of ciprofloxacin.
• Assessment of type I collagen production, assembly, hydroxyproline content, fibronectin production, lysyl oxidase activity, collagen fibril characteristics, and β1-integrin expression.

Main Results:

• Ciprofloxacin is taken up by mouse tendon cells via carrier-mediated transport.
• FQ antibiotics downregulated type I collagen production, assembly, and hydroxyproline content.
• Reduced fibronectin production, lysyl oxidase activity, collagen fibril stiffness and diameter, and active β1-integrin expression were observed.

Conclusions:

• Fluoroquinolones negatively impact key components of tendon extracellular matrix, including type I collagen and fibronectin.
• Decreased fibronectin and active β1-integrin expression suggest anoikis as a potential mechanism in FQ-induced tendinopathy.
• These findings provide insight into the pathological basis of FQ-associated tendinopathy.