Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Jiawei Guo; Fuxiao Wang; Yan Hu; Ying Luo; Yan Wei; Ke Xu; Hao Zhang; Han Liu; Lumin Bo; Shunli Lv; Shihao Sheng; Xinchen Zhuang; Tao Zhang; Can Xu; Xiao Chen; Jiacan Su

doi:10.1016/j.xcrm.2022.100881

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Cell Rep Med. 2023 Jan 17;4(1):100881. doi: 10.1016/j.xcrm.2022.100881. Epub 2023 Jan 4.

Authors

Jiawei Guo¹, Fuxiao Wang², Yan Hu², Ying Luo³, Yan Wei², Ke Xu², Hao Zhang², Han Liu², Lumin Bo⁴, Shunli Lv⁴, Shihao Sheng³, Xinchen Zhuang³, Tao Zhang³, Can Xu⁵, Xiao Chen⁶, Jiacan Su⁷

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
² Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
³ Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
⁴ Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
⁵ Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China. Electronic address: xxcc211@126.com.
⁶ Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China. Electronic address: sirchenxiao@126.com.
⁷ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Organoid Research Center, Shanghai University, Shanghai 200444, China. Electronic address: drsujiacan@163.com.

Abstract

Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) with unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium and IL-10 knockout induced with piroxicam, bone mass and quality are significantly decreased. Colitis mice demonstrate a lower bone formation rate and fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis mice tend to differentiate into adipocytes rather than osteoblasts. Serum from patients with IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that colitis downregulates Wnt signaling in BMSCs. For treatment, exosomes with Golgi glycoprotein 1 inserted could carry Wnt agonist 1 and accumulate in bone via intravenous administration. They could alleviate bone loss, promote bone formation, and accelerate fracture healing in colitis mice. Collectively, BMSC commitment in inflammatory microenvironment contributes to lower bone quantity and quality and could be rescued by redirecting differentiation toward osteoblasts through bone-targeted drug delivery.

Keywords: exosome; inflammatory bowel diseases; mesenchymal stem cell; osteoblastic formation; osteogenesis.

Publication types

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

MeSH terms

Animals
Cell Differentiation
Colitis* / chemically induced
Colitis* / drug therapy
Drug Delivery Systems / methods
Exosomes*
Humans
Inflammatory Bowel Diseases* / complications
Inflammatory Bowel Diseases* / drug therapy
Mice
Osteogenesis* / drug effects