IADR Abstract Archives
Neuropeptide Regulates Immune Response-mediated Implant Osseointegration by YAP Signaling
Objectives: The representative neuropeptide calcitonin gene-related peptide (CGRP) is expected to regulate a series of biological behavior of macrophages, which are one of the most diverse immune cells in peri-implant wound tissue. However, the intrinsic mechanism of immune response-mediated osseointegration by CGRP has not yet been clarified. In addition, latest researches indicate that CGRP’s receptor belongs to G protein-coupled receptor (GPCR), which is expected to be the upstream of Hippo-YAP pathway in regulating osteogenesis of bone-related cells. Therefore, this study aims to investigate whether CGRP regulates immune response-mediated osteogenesis and implant osseointegration by YAP signaling.
Methods: CGRP-/- mice and wild-type mice (C57BL/6) were used to explore the effects of different levels of CGRP on polarization of bone marrow derived macrophages (BMDMs) in vitro and the regulation of implant osseointegration in vivo. To further investigate the mechanism of CGRP-regulated osteogenesis, CGRP’s receptor, receptor activity-modifying protein-1 (RAMP1), was introduced to explore its role and intrinsic mechanism in regulating YAP signaling thus mediating bone metabolism.
Results: In vitro, knocking out CGRP gene can promote M1 phenotype and inhibit M2 phenotype expression of BMDMs, but it is close to wild-type expression after adding CGRP, suggesting that CGRP is involved in polarization of macrophages. In vivo, CGRP deficiency might influence osseointegration, and CGRP recovery with lentivirus transfection might improve osseointegration and reduce inflammation infiltration in a continuous and effective manner. Furthermore, transfection of RAMP1 into mouse MSCs showed that RAMP1 regulated MSCs migration, functional osteogenesis and phenotype expression through YAP signaling.
Conclusions: CGRP can promote osseointegration of implants and regulate M1 and M2 polarization of macrophages. Its receptor RAMP1 may regulate the osteogenesis of MSCs by activating downstream YAP signaling, suggesting that CGRP may be one of the key factors in the neuro-immune-bone metabolic regulatory network.
Methods: CGRP-/- mice and wild-type mice (C57BL/6) were used to explore the effects of different levels of CGRP on polarization of bone marrow derived macrophages (BMDMs) in vitro and the regulation of implant osseointegration in vivo. To further investigate the mechanism of CGRP-regulated osteogenesis, CGRP’s receptor, receptor activity-modifying protein-1 (RAMP1), was introduced to explore its role and intrinsic mechanism in regulating YAP signaling thus mediating bone metabolism.
Results: In vitro, knocking out CGRP gene can promote M1 phenotype and inhibit M2 phenotype expression of BMDMs, but it is close to wild-type expression after adding CGRP, suggesting that CGRP is involved in polarization of macrophages. In vivo, CGRP deficiency might influence osseointegration, and CGRP recovery with lentivirus transfection might improve osseointegration and reduce inflammation infiltration in a continuous and effective manner. Furthermore, transfection of RAMP1 into mouse MSCs showed that RAMP1 regulated MSCs migration, functional osteogenesis and phenotype expression through YAP signaling.
Conclusions: CGRP can promote osseointegration of implants and regulate M1 and M2 polarization of macrophages. Its receptor RAMP1 may regulate the osteogenesis of MSCs by activating downstream YAP signaling, suggesting that CGRP may be one of the key factors in the neuro-immune-bone metabolic regulatory network.
