Mineralised collagen regulated the secretion of adrenomedullin by macrophages to activate the PI3K/AKT signalling pathway to promote bone defect repair

Chunxiu Meng; Xin Luo; Jun Li; Yujue Zhang; Zhaoyong Lv; Caiyao Hou; Kun Liu; Fengzhen Liu

doi:10.1016/j.ijbiomac.2024.131800

Mineralised collagen regulated the secretion of adrenomedullin by macrophages to activate the PI3K/AKT signalling pathway to promote bone defect repair

Int J Biol Macromol. 2024 Apr 26;269(Pt 2):131800. doi: 10.1016/j.ijbiomac.2024.131800. Online ahead of print.

Authors

Chunxiu Meng¹, Xin Luo¹, Jun Li¹, Yujue Zhang¹, Zhaoyong Lv¹, Caiyao Hou², Kun Liu³, Fengzhen Liu⁴

Affiliations

¹ Liaocheng People's Hospital, Liaocheng Hospital Affiliated Shandong First Medical University, Liaocheng 252000, China.
² Department of Materials Science and Engineering, Liaocheng University, Liaocheng 252000, China.
³ Liaocheng People's Hospital, Liaocheng Hospital Affiliated Shandong First Medical University, Liaocheng 252000, China. Electronic address: 827825736@qq.com.
⁴ Liaocheng People's Hospital, Liaocheng Hospital Affiliated Shandong First Medical University, Liaocheng 252000, China. Electronic address: LDCLLFZ@163.com.

PMID: 38679262
DOI: 10.1016/j.ijbiomac.2024.131800

Abstract

Biomaterials can affect the osteogenic process by regulating the function of macrophages and transforming the bone immune microenvironment. Mineralised collagen (MC) is an artificial bone that is highly consistent to the microstructure of the native osseous matrix. The studies have confirmed that MC can achieve effective regeneration of bone defects, but the potential mechanism of MC regulating osteogenesis is still unclear. This study confirmed that MC regulate the high expression of adrenomedullin (ADM) in macrophages and promote the osteogenic differentiation, proliferation and migration of BMSCs. Moreover, ADM activated the PI3K/Akt pathway, while the inhibition of PI3K/Akt hindered the proliferation, migration and osteogenic differentiation of BMSCs promoted by ADM. Additionally, the rat mandibular defect model confirmed that ADM promote the repair of mandibular defects, and the inhibition of PI3K/Akt pathway hinders the osteogenic effect of ADM. Our study suggests that MC regulates ADM secretion by macrophages, creates an ideal bone immune microenvironment, activates the PI3K/AKT signalling pathway, and promotes osteogenesis.

Keywords: Adrenomedullin; Jawbone defect repair; Macrophage; Mineralised collagen; PI3K/AKT signalling pathway.