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.

Bone Research
|September 14, 2018
PubMed

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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