title: Effect of bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres on bone and joint tuberculosis in vitro.
abstract: Rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (RPMs)-loaded bone-like hydroxyapatite/poly amino acid (BHA/PAA) is effective in curing Staphylococcus aureus-induced chronic osteomyelitis. This study continues to investigate the effect of RPM-loaded BHA/PAA on the bacterial growth of Mycobacterium tuberculosis (MTB), cell proliferation and differentiation in MTB H37Rv-infected MG63 cells. Furthermore, whether Wnt/β-catenin signaling pathway was activated by RPM-loaded BHA/PAA was explored. We found the bactec growth index of H37Rv was significantly inhibited by RPM-loaded BHA/PAA. The MTT assay showed that RPM-loaded BHA/PAA could promote the cell proliferation of H37Rv-infected MG63 cells, as determined by MTT assay. The alkaline phosphatase (ALP) activity and the expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) was examined by commercial kit and Western blot analysis to determine the effect of RPM-loaded BHA/PAA on MTB H37Rv-infected MG63 cell differentiation. It was revealed that RPM-loaded BHA/PAA could promote cell differentiation of H37Rv-infected MG63 cells. Furthermore, we found the expression of Wnt1, LDL receptor related protein 6 (Lrp6) and β-catenin was significantly increased in H37Rv-infected MG63 cells following treatment with RPM-loaded BHA/PAA, as determined by Western blot analysis. In conclusion, this study demonstrated that RPM-loaded BHA/PAA has an effective activity against MTB. RPM-loaded BHA/PAA promoted cell proliferation and cell differentiation of H37Rv-infected MG63 cells. Wnt/β-catenin signaling could be activated by RPM-loaded BHA/PAA in MG63 cells infected with H37Rv. This study demonstrated the potential value of RPM-loaded BHA/PAA in treating bone and joint TB, and suggested Wnt/β-catenin signaling may be an important pathway underlying its function.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
authors.forename: Dianming
authors.initials: D
authors.lastname: Jiang
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000494:pharmacology*; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014394:Tuberculosis, Osteoarticular / Q000188:drug therapy*; D060449:Wnt Signaling Pathway
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite; D012293:Rifampin; C018421:rifapentine
keywords: RPM-loaded BHA/PAA; bacterial growth; bone and joint tuberculosis; differentiation; proliferation