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.
Copyright © 2017 Elsevier Inc. All rights reserved.
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