Loss Of Stat3 In Prx1+ Progenitors Impairs Molar Root Development

Signal Transducer and Activator of Transcription 3 (Stat3) serves as a pivotal transcriptional regulator implicated in cell proliferation, survival, apoptosis, angiogenesis, immune response, and cell migration. Loss of Stat3 in human leads to Hyper-IgE syndrome, leading to immune system dysfunction, skeletal abnormalities, and dental anomalies. In the present study, transgenic mice were utilized to explore the potential mechanisms of Stat3 in mesenchymal progenitors on the development of molar roots and periodontal tissue. Transgenic mice with conditional knockout (CKO) of Stat3(Prx1-Cre; Stat3f/f) were constructed. We compared the difference in molar root development between the control group and Stat3 CKO mice using histological analysis, Micro-CT, cytological experiments, and RNA sequencing. Compared with control, Stat3 CKO mice exhibited pronounced abnormalities in their first molar phenotype, characterized by a shorter root and an increased crown-to-root ratio. In the periodontal tissue of Stat3 CKO mice, the periodontal ligament (PDL) at the distal root of the first molar became narrowed. The expressions of osteogenesis-related proteins, including Runx2, Col1a1, and Ocn, in the alveolar bone were down-regulated, as were the cellular counts positive for Ki67 and BrdU within the PDL. The development of the mandibular first molars and alveolar bone in mice is significantly influenced by Stat3. In both in vivo and in vitro settings, the absence of Stat3 leads to the impairment of osteogenesis in Paired related homeobox 1(Prx1+) progenitor cells.