摘要
Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRNAs), from donors to receptors.MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1(Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth development.More importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133 b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.
Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRNAs), from donors to receptors.MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1(Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth development.More importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133 b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.
基金
supported by the National Natural Science Foundation of China (No. 91649124 to S.W.
No. 81371108 and 81670955 to A.L. and No. 81701037 to Y.L.)
Beijing Municipality Government grants (Beijing Scholar ProgramPXM2016_014226_000006, PXM2016_014226_000034, PXM2015_014226_000052, PXM2015_014226_000055, PXM2015_014226_000116, PXM2014_014226_000013, PXM2014_014226_000048, PXM2014_014226_000053, Z121100005212004, PXM2013_014226_000021, PXM2013_014226_000055, PXM 2013_014226_07_ 000080 and TJSHG201310025005 to S.W.)
an Open grant from Capital Medical University (No. KFKT2016005 to Y.L.)
