Anti-tuberculosis drugs decrease viability and stimulate the expression of chondrocyte marker genes in human nucleus pulposus cells

Abstract

Isoniazid (INH), rifampicin (RIF), ethambutol (ETH) and pyrazinamide (PYR) are first‑line drugs used in anti‑tuberculosis (TB) therapy. However, no studies have been conducted concerning the effect of anti‑TB drugs on the cells of the intervertebral discs (IVDs), the predominant location of the osteoarticular form of TB (OATB). Cells from the nucleus pulposus (NP), which are located in the center of the IVDs, were obtained from 12 adolescent patients who underwent surgery due to idiopathic scoliosis. The NP cells were incubated for 24h with transforming growth factorβ1 (TGF‑β1) and each anti‑TB drug (INH, RIF, ETH and PYR), separately. Incubation with 2.5ng/ml TGF‑β1 resulted in an 80% decrease in ACAN mRNA levels; while 5µg/ml INH led to a 2.3‑fold increase in COL2A1 and a 2.9‑fold increase in ACAN mRNA levels. Treatment with 10µg/ml RIF initiated a 2.2‑fold increase in COL1A1 mRNA levels and 5µg/ml PYR resulted in an 8‑fold increase in SOX9 mRNA levels. Following 192h of treatment with INH and RIF, NP cell viability was diminished; however, no drugs modified the concentrations of glycosaminoglycans (GAGs). This study aimed to determine the effect of anti‑TB drugs on the expression of chondrocyte marker genes in human IVD cells. Anti‑TB drugs increased the expression of chondrocyte marker genes and diminished the viability of IVD cells. This study demonstrated that in addition to the common side effects of anti‑TB drugs, these drugs also have an effect on IVD cells.