Effect of bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres on bone and joint tuberculosis in vitro

Cell Biol Int. 2017 Apr;41(4):369-373. doi: 10.1002/cbin.10730. Epub 2017 Feb 27.

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.

Keywords: RPM-loaded BHA/PAA; bacterial growth; bone and joint tuberculosis; differentiation; proliferation.

MeSH terms

  • Cell Differentiation
  • Cell Line, Tumor
  • Drug Carriers / pharmacology*
  • Durapatite / chemistry*
  • Humans
  • Lactic Acid / chemistry*
  • Microbial Sensitivity Tests
  • Microspheres
  • Mycobacterium tuberculosis / drug effects*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rifampin / analogs & derivatives*
  • Rifampin / pharmacology
  • Tuberculosis, Osteoarticular / drug therapy*
  • Wnt Signaling Pathway

Substances

  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Durapatite
  • Rifampin
  • rifapentine