Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis

Yuan Zhu; Kunkun Yang; Yawen Cheng; Yaoshan Liu; Ranli Gu; Xuenan Liu; Hao Liu; Xiao Zhang; Yunsong Liu

doi:10.1002/smll.202205813

Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis

Small. 2023 Apr;19(16):e2205813. doi: 10.1002/smll.202205813. Epub 2023 Jan 20.

Authors

Yuan Zhu^{1

2}, Kunkun Yang¹, Yawen Cheng¹, Yaoshan Liu¹, Ranli Gu¹, Xuenan Liu¹, Hao Liu³, Xiao Zhang^{1

2}, Yunsong Liu^{1

2}

Affiliations

¹ Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Beijing, 100081, China.
² National Center of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
³ The Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Beijing, 100081, China.

PMID: 36670083
DOI: 10.1002/smll.202205813

Abstract

Mesenchymal stem cells (MSCs) are widely used in the treatment of diseases. After their in vivo application, MSCs undergo apoptosis and release apoptotic vesicles (apoVs). This study investigates the role of apoVs derived from human bone marrow mesenchymal stem cells (hBMMSCs) in bone metabolism and the molecular mechanism of the observed effects. The results show that apoVs can promote osteogenesis and inhibit osteoclast formation in vitro and in vivo. ApoVs may therefore attenuate the bone loss caused by primary and secondary osteoporosis and stimulate bone regeneration in areas of bone defect. The mechanisms responsible for apoV-induced bone regeneration include the release of miR1324, which inhibit expression of the target gene Sorting Nexin 14 (SNX14) and thus activate the SMAD1/5 pathway in target cells. Given that MSC-derived apoVs are easily obtained and stored, with low risks of immunological rejection and neoplastic transformation, The findings suggest a novel therapeutic strategy to treat bone loss, including via cell-free approaches to bone tissue engineering.

Keywords: apoptotic vesicles; bone metabolism; cell-free therapy; miR1324/SNX14/SMAD1/5 signaling axis.

Publication types

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

MeSH terms

Bone Regeneration
Bone and Bones
Cell Differentiation / physiology
Humans
Mesenchymal Stem Cells* / metabolism
Osteogenesis
Signal Transduction*
Sorting Nexins / metabolism

Substances

SNX14 protein, human
Sorting Nexins