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Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis
Ye Li1,2, Xinxin Wang2, Jiali Ren2
11Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.
Abstract:
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-133b 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.
Insights
Mandible exosomes carrying microRNA-133b trigger apoptosis in dental cells, hindering maxillofacial development and tooth formation. This study reveals a novel mechanism in exosome-mediated signal transduction during development.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Exosomes mediate intercellular communication by transferring microRNAs (miRNAs).
- MiRNAs regulate diverse biological processes, including maxillofacial development.
- The specific mechanisms of miRNA-mediated signaling in maxillofacial development are not fully understood.
Purpose of the Study:
- To investigate the role of specific miRNAs and exosomes in maxillofacial development.
- To identify the molecular targets and pathways involved in miRNA-induced apoptosis in dental cells.
- To elucidate the function of mandible-derived exosomes in tooth formation.
Main Methods:
- Expression analysis of ssc-mir-133b in miniature swine maxillofacial tissues.
- In vitro studies on primary dental mesenchymal cells to assess apoptosis.
- Identification of the functional target of ssc-mir-133b using molecular assays.
- In vivo animal study involving subcutaneous transplantation of cells with ectopic ssc-mir-133b expression in nude mice.
Main Results:
- Upregulation of ssc-mir-133b induced significant apoptosis in dental mesenchymal cells.
- Cell leukemia myeloid 1 (Mcl-1) was identified as a direct functional target of ssc-mir-133b.
- Mandible exosomes were confirmed as carriers of the apoptosis-inducing signal.
- Ectopic ssc-mir-133b expression in vivo led to abnormal tooth germ development and failed tooth formation.
Conclusions:
- Mandible exosomes play a critical role in transmitting developmental signals via miRNAs like ssc-mir-133b.
- Ssc-mir-133b induces apoptosis in dental cells by targeting Mcl-1, impacting tooth development.
- Disruption of exosomal signaling by ssc-mir-133b impairs normal maxillofacial development and tooth formation.
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