Catalpol modulating the crosstalking between mesenchymal stromal cells and macrophages via paracrine to enhance angiogenesis and osteogenesis

Yanling Zhang; Zhiyun Du; Dan Li; Zhuo Wan; Tianyi Zheng; Xuehui Zhang; Yingjie Yu; Xiaoping Yang; Qing Cai

doi:10.1016/j.yexcr.2022.113269

Catalpol modulating the crosstalking between mesenchymal stromal cells and macrophages via paracrine to enhance angiogenesis and osteogenesis

Exp Cell Res. 2022 Sep 15;418(2):113269. doi: 10.1016/j.yexcr.2022.113269. Epub 2022 Jul 8.

Authors

Yanling Zhang¹, Zhiyun Du², Dan Li¹, Zhuo Wan³, Tianyi Zheng¹, Xuehui Zhang⁴, Yingjie Yu⁵, Xiaoping Yang², Qing Cai⁶

Affiliations

¹ State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
² State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China; Foshan (Southern China) Institute for New Materials, Foshan, 528200, Guangdong, PR China.
³ State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China; Department of Mechanics and Engineering Science, Beijing Innovation Center for Engineering Science and Advanced Technology, College of Engineering, Peking University, Beijing, 100871, China.
⁴ Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
⁵ State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China. Electronic address: yuyingjie@mail.buct.edu.cn.
⁶ State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China. Electronic address: caiqing@mail.buct.edu.cn.

PMID: 35817196
DOI: 10.1016/j.yexcr.2022.113269

Abstract

Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration. It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation, promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.

Keywords: Bone regeneration; Catalpol; Immunoregulation; Paracrine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Iridoid Glucosides / pharmacology
Macrophages
Mesenchymal Stem Cells*
Osteogenesis*

Substances

Iridoid Glucosides
catalpol