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Area of Science:

  • Biomedical Sciences
  • Cell Biology
  • Pharmacology

Background:

  • Tuberculosis (TB) affects bones, but the impact of anti-TB drugs on intervertebral disc (IVD) cells is unknown.
  • Nucleus pulposus (NP) cells are central to IVD health and function.
  • Osteoarticular TB (OATB) predominantly affects the spine, highlighting the need to understand drug effects on IVD cells.

Purpose of the Study:

  • To investigate the effects of first-line anti-tuberculosis drugs on human nucleus pulposus (NP) cells.
  • To determine the impact of isoniazid (INH), rifampicin (RIF), ethambutol (ETH), and pyrazinamide (PYR) on chondrocyte marker gene expression in IVD cells.
  • To assess the influence of these drugs on NP cell viability and glycosaminoglycan (GAG) production.

Main Methods:

  • Human NP cells were isolated from adolescent idiopathic scoliosis patients.
  • Cells were incubated with transforming growth factor-β1 (TGF-β1) and individual anti-TB drugs (INH, RIF, ETH, PYR).
  • Gene expression (ACAN, COL2A1, COL1A1, SOX9) and cell viability were analyzed after 24 and 192 hours, respectively. GAG concentrations were also measured.

Main Results:

  • Transforming growth factor-β1 significantly decreased ACAN mRNA levels.
  • Isoniazid increased COL2A1 and ACAN mRNA.
  • Rifampicin increased COL1A1 mRNA, and Pyrazinamide increased SOX9 mRNA.
  • Prolonged exposure to isoniazid and rifampicin reduced NP cell viability.
  • No significant changes in glycosaminoglycan concentrations were observed.

Conclusions:

  • First-line anti-tuberculosis drugs modulate chondrocyte marker gene expression in human IVD cells.
  • Isoniazid and rifampicin can negatively impact NP cell viability.
  • These findings suggest potential adverse effects of anti-TB drugs on intervertebral disc health beyond known systemic side effects.