Combination of PTH (1-34) with anti-IL17 prevents bone loss by inhibiting IL-17/N-cadherin mediated disruption of PTHR1/LRP-6 interaction

Bone. 2017 Dec:105:226-236. doi: 10.1016/j.bone.2017.09.010. Epub 2017 Sep 19.

Abstract

Combinations of anabolic and anti-resorptive agents have potential to improve bone density more than either agent alone. In this study, we determine the combining effect of anti-IL17 antibody and PTH (1-34) in mitigation of ovariectomy induced bone loss. Ovariectomized BALB/c female mice were treated with anti-IL17 and iPTH monotherapies and their combination. Combination of iPTH and anti-IL17 has synergistic effect in the restoration of skeletal and immune parameters compared to mono-therapies. Immunofluorescence analysis shows decreased expression of PTHR1 in iPTH+anti-IL17 treated bone sections. Our studies show that IL-17 up regulates N-cadherin which disrupts PTHR1/LRP-6 interaction thereby inhibiting wnt signaling and promoting bone loss. Our studies advocate use of iPTH and anti-IL17 combination therapy for post-menopausal osteoporosis.

Keywords: IL-17A; Osteoimmunology; Osteoporosis; PTH.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / drug therapy
  • Bone Resorption / pathology
  • Bone Resorption / prevention & control*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cadherins / metabolism*
  • Cell Differentiation / drug effects
  • Cortical Bone / diagnostic imaging
  • Cortical Bone / drug effects
  • Cortical Bone / pathology
  • Drug Therapy, Combination
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / pathology
  • Inflammation Mediators / metabolism
  • Interleukin-17 / antagonists & inhibitors*
  • Low Density Lipoprotein Receptor-Related Protein-6 / metabolism*
  • Mice, Inbred BALB C
  • Models, Biological
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone / therapeutic use*
  • Peptide Fragments / metabolism
  • Procollagen / metabolism
  • Protein Binding / drug effects
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • X-Ray Microtomography

Substances

  • Biomarkers
  • Cadherins
  • Inflammation Mediators
  • Interleukin-17
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Parathyroid Hormone
  • Peptide Fragments
  • Procollagen
  • Receptor, Parathyroid Hormone, Type 1
  • procollagen Type I N-terminal peptide
  • Tartrate-Resistant Acid Phosphatase