CXCL chemokines-mediated communication between macrophages and BMSCs on titanium surface promotes osteogenesis via the actin cytoskeleton pathway

Yayun Zhang; Jiemao Wei; Xingbang Yu; Liangxi Chen; Ranyue Ren; Yimin Dong; Sibo Wang; Meipeng Zhu; Nannan Ming; Ziwei Zhu; Chenghao Gao; Wei Xiong

doi:10.1016/j.mtbio.2023.100816

CXCL chemokines-mediated communication between macrophages and BMSCs on titanium surface promotes osteogenesis via the actin cytoskeleton pathway

Mater Today Bio. 2023 Oct 5:23:100816. doi: 10.1016/j.mtbio.2023.100816. eCollection 2023 Dec.

Authors

Yayun Zhang^{1

2}, Jiemao Wei¹, Xingbang Yu¹, Liangxi Chen¹, Ranyue Ren¹, Yimin Dong¹, Sibo Wang¹, Meipeng Zhu¹, Nannan Ming³, Ziwei Zhu¹, Chenghao Gao¹, Wei Xiong¹

Affiliations

¹ Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
² Trauma Center/Department of Emergency and Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
³ The State Key Laboratory of Refractories and Metallurgy Institute of Advanced Materials and Nanotechnology Wuhan University of Science and Technology, Wuhan, 430081, China.

Abstract

The refined functional cell subtypes in the immune microenvironment of specific titanium (Ti) surface and their collaborative role in promoting bone marrow mesenchymal stem cells (BMSCs) driven bone integration need to be comprehensively characterized. This study employed a simplified co-culture system to investigate the dynamic, temporal crosstalk between macrophages and BMSCs on the Ti surface. The M2-like sub-phenotype of macrophages, characterized by secretion of CXCL chemokines, emerges as a crucial mediator for promoting BMSC osteogenic differentiation and bone integration in the Ti surface microenvironment. Importantly, these two cells maintain their distinct functional phenotypes through a mutually regulatory interplay. The secretion of CXCL3, CXCL6, and CXCL14 by M2-like macrophages plays a pivotal role. The process activates CXCR2 and CCR1 receptors, triggering downstream regulatory effects on the actin cytoskeleton pathway within BMSCs, ultimately fostering osteogenic differentiation. Reciprocally, BMSCs secrete pleiotrophin (PTN), a key player in regulating macrophage differentiation. This secretion maintains the M2-like phenotype via the Sdc3 receptor-mediated cell adhesion molecules pathway. Our findings provide a novel insight into the intricate communication and mutual regulatory mechanisms operating between BMSCs and macrophages on the Ti surface, highlight specific molecular events governing cell-cell interactions in the osteointegration, inform the surface design of orthopedic implants, and advance our understanding of osteointegration.

Keywords: Bone mesenchymal stem cells; Cell-cell communication; Chemokines; Macrophages; Osteointegration.