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

Lehmann,Tomasz  P.; Głowacki,Maciej; Misterska,Ewa; Walczak,Michał; Jagodziński,Paweł  P.; Głowacki,Jakub

doi:10.3892/mmr.2013.1767

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

Authors:
- Tomasz P. Lehmann
- Maciej Głowacki
- Ewa Misterska
- Michał Walczak
- Paweł P. Jagodziński
- Jakub Głowacki
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Affiliations: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60‑781, Poland, Department of Pediatric Orthopaedics and Traumatology, Poznań University of Medical Sciences, Poznań 61‑545, Poland, SSG of Paediatric Orthopaedics and Traumatology, Department of Paediatric Orthopaedics and Traumatology, Poznań University of Medical Sciences, Poznań 61‑545, Poland
Published online on: October 30, 2013 https://doi.org/10.3892/mmr.2013.1767
Pages: 316-322

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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 24 h with transforming growth factor β1 (TGF‑β1) and each anti‑TB drug (INH, RIF, ETH and PYR), separately. Incubation with 2.5 ng/ml TGF‑β1 resulted in an 80% decrease in ACAN mRNA levels; while 5 µg/ml INH led to a 2.3‑fold increase in COL2A1 and a 2.9‑fold increase in ACAN mRNA levels. Treatment with 10 µg/ml RIF initiated a 2.2‑fold increase in COL1A1 mRNA levels and 5 µg/ml PYR resulted in an 8‑fold increase in SOX9 mRNA levels. Following 192 h 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.

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