https://orcid.org/0009-0004-4009-4942
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Abstract
Aim: To determine the mechanism of Calcitonin gene-related peptide (CGRP) in bone healing. Materials & methods: Alkaline phosphatase (ALP) activity and inflammatory-factor levels were detected using ELISA. Osteogenic differentiation was assessed using Alizarin red staining technique. The interaction between histone deacetylase 6 (HDAC6) and A-kinase anchoring protein 12 (AKAP12) was investigated through Co- immunoprecipitation. Results: CGRP treatment promoted rat bone marrow-derived macrophages (BMDMs) M2 polarization. CGRP facilitated osteogenic differentiation by enhancing M2 polarization of BMDMs. Mechanistically, CGRP promoted AKAP12 acetylation to activate the extracellular regulated protein kinases pathway by HDAC6 inhibition. Conclusion: CGRP promoted M2 polarization of rat BMDMs and facilitated osteogenic differentiation through the HDAC6/AKAP12/extracellular regulated protein kinases signaling pathway, thereby promoting bone healing.
GRAPHICAL ABSTRACT
Diverse concentrations of calcitonin gene-related peptide (CGRP) induced M2 polarization in rat macrophages.
CGRP promoted osteogenic differentiation after co-culture of rat macrophages and rat osteoblasts.
With the increase in CGRP concentration, there was a gradual downregulation of histone deacetylase 6 expression.
CGRP promoted M2 polarization of rat bone marrow-derived macrophages and facilitated osteogenic differentiation through histone deacetylase 6/A-kinase anchoring protein 12/extracellular regulated protein kinases signaling pathway, thereby promoting bone healing.
The present findings offer a theoretical basis for clinical interventions in fracture healing.
Author contributions
WC and XJ designed this study. WC, LM, WS, WX, HG and JX collected the materials and performed the experiments. WC analyzed the data and wrote the manuscript. XJ revised the manuscript. All authors read and approved the final version of the manuscript.
Financial disclosure
This work was supported by Heilongjiang Provincial Health Commission (20210404070196). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval (QMU-AECC-2021-81) and/or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.