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Int J Mol Sci. 2019 Jan 24;20(3). pii: E503. doi: 10.3390/ijms20030503.

Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages.

Author information

1
Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, University of Regensburg, 93053 Regensburg, Germany. dominique.muschter@ukr.de.
2
Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, University of Regensburg, 93053 Regensburg, Germany. anna-sophie.b@arcor.de.
3
Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, University of Regensburg, 93053 Regensburg, Germany. tanja.spaeth@ukr.de.
4
Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany. christian.kirschneck@ukr.de.
5
Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany. agnes.schroeder@ukr.de.
6
Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, University of Regensburg, 93053 Regensburg, Germany. susanne.graessel@ukr.de.

Abstract

This study aimed to analyze if the sensory neuropeptide SP (SP) and the neurokinin receptor 1 (NK1R) are involved in macrophage mechano-transduction, similar to chondrocytes, and if alpha-calcitonin gene-related peptide (αCGRP) and the CGRP receptor (CRLR/Ramp1) show comparable activity. Murine RAW264.7 macrophages were subjected to a cyclic stretch for 1⁻3 days and 4 h/day. Loading and neuropeptide effects were analyzed for gene and protein expression of neuropeptides and their receptors, adhesion, apoptosis, proliferation and ROS activity. Murine bone marrow-derived macrophages (BMM) were isolated after surgical osteoarthritis (OA) induction and proliferation, apoptosis and osteoclastogenesis were analyzed in response to loading. Loading induced NK1R and CRLR/Ramp1 gene expression and altered protein expression in RAW264.7 macrophages. SP protein and mRNA level decreased after loading whereas αCGRP mRNA expression was stabilized. SP reduced adhesion in loaded RAW264.7 macrophages and both neuropeptides initially increased the ROS activity followed by a time-dependent suppression. OA induction sensitized BMM to caspase 3/7 mediated apoptosis after loading. Both sensory neuropeptides, SP and αCGRP, and their receptors are involved in murine macrophage mechano-transduction affecting neuropeptide impact on adhesion and ROS activity. OA induction altered BMM apoptosis in response to loading indicate that OA-associated biomechanical alterations might affect the macrophage population.

KEYWORDS:

CGRP receptor; alpha-calcitonin gene-related peptide; cyclic stretch; destabilized medial meniscus; mechan-oregulation; murine macrophages; neurokinin receptor; substance P

PMID:
30682804
PMCID:
PMC6386869
DOI:
10.3390/ijms20030503
[Indexed for MEDLINE]
Free PMC Article

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