Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study
Abstract Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation, a combination drug therapy with a bone anabolic agent could help in fracture prevention and promote bone reconstruction....
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| Format: | Article |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25174-6 |
| _version_ | 1811198377096904704 |
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| author | Subum Lee Ye-Jin Seo Je-Yong Choi Xiangguo Che Hyun-Ju Kim Seok-Yong Eum Min-Sun Hong Sun-Kyoung Lee Dae-Chul Cho |
| author_facet | Subum Lee Ye-Jin Seo Je-Yong Choi Xiangguo Che Hyun-Ju Kim Seok-Yong Eum Min-Sun Hong Sun-Kyoung Lee Dae-Chul Cho |
| author_sort | Subum Lee |
| collection | DOAJ |
| description | Abstract Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation, a combination drug therapy with a bone anabolic agent could help in fracture prevention and promote bone reconstruction. This study aimed to investigate the influence of teriparatide on the effect of anti-tuberculous drugs in tuberculous spondylitis treatment. We used the virulent Mycobacterium tuberculosis (Mtb) H37Rv strain. First, we investigated the interaction between teriparatide and anti-tuberculosis drugs (isoniazid and rifampin) by measuring the minimal inhibitory concentration (MIC) against H37Rv. Second, we evaluated the therapeutic effect of anti-tuberculosis drugs and teriparatide on our previously developed in vitro tuberculous spondylitis model of an Mtb-infected MG-63 osteoblastic cell line using acid-fast bacilli staining and colony-forming unit counts. Selected chemokines (interleukin [IL]-8, interferon γ-induced protein 10 kDa [IP-10], monocyte chemoattractant protein [MCP]-1, and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]) and osteoblast proliferation (alkaline phosphatase [ALP] and alizarin red S [ARS] staining) were measured. Teriparatide did not affect the MIC of isoniazid and rifampin. In the Mtb-infected MG-63 spondylitis model, isoniazid and rifampin treatment significantly reduced Mtb growth, and cotreatment with teriparatide did not change the anti-tuberculosis effect of isoniazid (INH) and rifampin (RFP). IP-10 and RANTES levels were significantly increased by Mtb infection, whereas teriparatide did not affect all chemokine levels as inflammatory markers. ALP and ARS staining indicated that teriparatide promoted osteoblastic function even with Mtb infection. Cotreatment with teriparatide and the anti-tuberculosis drugs activated bone formation (ALP-positive area increased by 705%, P = 0.0031). Teriparatide was effective against Mtb-infected MG63 cells without the anti-tuberculosis drugs (ARS-positive area increased by 326%, P = 0.0037). Teriparatide had no effect on the efficacy of anti-tuberculosis drugs and no adverse effect on the activity of Mtb infection in osteoblasts. Furthermore, regulation of representative osteoblastic inflammatory chemokines was not changed by teriparatide treatment. In the in vitro Mtb-infected MG-63 cell model of tuberculous spondylitis, cotreatment with the anti-tuberculosis drugs and teriparatide increased osteoblastic function. |
| first_indexed | 2024-04-12T01:29:53Z |
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| id | doaj.art-9cfce4f7039b4acbaa756b6f4a934946 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T01:29:53Z |
| publishDate | 2022-12-01 |
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| series | Scientific Reports |
| spelling | doaj.art-9cfce4f7039b4acbaa756b6f4a9349462022-12-22T03:53:31ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-25174-6Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental studySubum Lee0Ye-Jin Seo1Je-Yong Choi2Xiangguo Che3Hyun-Ju Kim4Seok-Yong Eum5Min-Sun Hong6Sun-Kyoung Lee7Dae-Chul Cho8Department of Neurosurgery, Korea University Anam Hospital, Korea University College of MedicineDepartment of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University HospitalDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National UniversityDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National UniversityDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National UniversityDivision of Immunopathology and Cellular Immunology, International Tuberculosis Research CenterDivision of Immunopathology and Cellular Immunology, International Tuberculosis Research CenterDivision of Immunopathology and Cellular Immunology, International Tuberculosis Research CenterDepartment of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University HospitalAbstract Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation, a combination drug therapy with a bone anabolic agent could help in fracture prevention and promote bone reconstruction. This study aimed to investigate the influence of teriparatide on the effect of anti-tuberculous drugs in tuberculous spondylitis treatment. We used the virulent Mycobacterium tuberculosis (Mtb) H37Rv strain. First, we investigated the interaction between teriparatide and anti-tuberculosis drugs (isoniazid and rifampin) by measuring the minimal inhibitory concentration (MIC) against H37Rv. Second, we evaluated the therapeutic effect of anti-tuberculosis drugs and teriparatide on our previously developed in vitro tuberculous spondylitis model of an Mtb-infected MG-63 osteoblastic cell line using acid-fast bacilli staining and colony-forming unit counts. Selected chemokines (interleukin [IL]-8, interferon γ-induced protein 10 kDa [IP-10], monocyte chemoattractant protein [MCP]-1, and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]) and osteoblast proliferation (alkaline phosphatase [ALP] and alizarin red S [ARS] staining) were measured. Teriparatide did not affect the MIC of isoniazid and rifampin. In the Mtb-infected MG-63 spondylitis model, isoniazid and rifampin treatment significantly reduced Mtb growth, and cotreatment with teriparatide did not change the anti-tuberculosis effect of isoniazid (INH) and rifampin (RFP). IP-10 and RANTES levels were significantly increased by Mtb infection, whereas teriparatide did not affect all chemokine levels as inflammatory markers. ALP and ARS staining indicated that teriparatide promoted osteoblastic function even with Mtb infection. Cotreatment with teriparatide and the anti-tuberculosis drugs activated bone formation (ALP-positive area increased by 705%, P = 0.0031). Teriparatide was effective against Mtb-infected MG63 cells without the anti-tuberculosis drugs (ARS-positive area increased by 326%, P = 0.0037). Teriparatide had no effect on the efficacy of anti-tuberculosis drugs and no adverse effect on the activity of Mtb infection in osteoblasts. Furthermore, regulation of representative osteoblastic inflammatory chemokines was not changed by teriparatide treatment. In the in vitro Mtb-infected MG-63 cell model of tuberculous spondylitis, cotreatment with the anti-tuberculosis drugs and teriparatide increased osteoblastic function.https://doi.org/10.1038/s41598-022-25174-6 |
| spellingShingle | Subum Lee Ye-Jin Seo Je-Yong Choi Xiangguo Che Hyun-Ju Kim Seok-Yong Eum Min-Sun Hong Sun-Kyoung Lee Dae-Chul Cho Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study Scientific Reports |
| title | Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study |
| title_full | Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study |
| title_fullStr | Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study |
| title_full_unstemmed | Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study |
| title_short | Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study |
| title_sort | effect of teriparatide on drug treatment of tuberculous spondylitis an experimental study |
| url | https://doi.org/10.1038/s41598-022-25174-6 |
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