Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis.
Yuan ZhuKunkun YangYawen ChengYaoshan LiuRanli GuXuenan LiuHao LiuXiao ZhangYunsong LiuPublished in: Small (Weinheim an der Bergstrasse, Germany) (2023)
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.
Keyphrases
- bone loss
- bone regeneration
- mesenchymal stem cells
- cell death
- cell free
- cell cycle arrest
- cell proliferation
- long non coding rna
- tissue engineering
- umbilical cord
- epithelial mesenchymal transition
- induced apoptosis
- bone mineral density
- endoplasmic reticulum stress
- endothelial cells
- oxidative stress
- transforming growth factor
- anti inflammatory
- postmenopausal women
- signaling pathway
- bone marrow
- gene expression
- combination therapy
- genome wide
- dna methylation
- risk assessment
- human health
- induced pluripotent stem cells
- room temperature
- high glucose
- circulating tumor cells
- circulating tumor
- ionic liquid