title: 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 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60‑781, Poland.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Lehmann
authors.forename: Maciej
authors.initials: M
authors.lastname: Głowacki
authors.forename: Ewa
authors.initials: E
authors.lastname: Misterska
authors.forename: Michał
authors.initials: M
authors.lastname: Walczak
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
authors.forename: Jakub
authors.initials: J
authors.lastname: Głowacki
mesh_terms: D000293:Adolescent; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000995:Antitubercular Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004977:Ethambutol / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007538:Isoniazid / Q000494:pharmacology; D011718:Pyrazinamide / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D000995:Antitubercular Agents; C499177:COL2A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D053773:Transforming Growth Factor beta1; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin