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Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway.

Shaoling Yu1, Qingming Tang1, Mengru Xie1

  • 1Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cell Proliferation
|November 21, 2019
PubMed
Summary
This summary is machine-generated.

Brain and muscle arnt-like 1 (BMAL1) is crucial for mandibular condylar cartilage development. BMAL1 deficiency impairs chondrogenesis and endochondral ossification, but this can be rescued by activating the hedgehog signaling pathway.

Keywords:
BMAL1chondrogenesis and endochondral ossificationgenome-wide RNA sequencingpatched homologue 1 (PTCH1)prepuberty and early puberty periods

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Chondrogenesis and endochondral ossification in the mandibular condyle are vital for facial development.
  • The circadian regulator BMAL1 is essential for embryonic and postnatal growth.

Purpose of the Study:

  • To investigate the role of BMAL1 in the growth of mandibular condylar cartilages (MCC).
  • To elucidate the molecular mechanisms by which BMAL1 influences MCC development.

Main Methods:

  • Utilized BMAL1-deficient mice models for in vivo studies.
  • Performed Micro-CT, TUNEL staining, and EdU assays.
  • Conducted in vitro experiments with rat chondrocytes and RNA sequencing for transcriptional profiling.

Main Results:

  • BMAL1 expression decreases with age in MCC.
  • BMAL1 deficiency impairs chondrocyte differentiation and endochondral ossification.
  • RNA sequencing identified the hedgehog signaling pathway as a key target of BMAL1.
  • BMAL1 directly regulates Ptch1 and Ihh gene expression, crucial for hedgehog signaling.
  • Phenotypic rescue of short stature was achieved by activating hedgehog signaling.

Conclusions:

  • BMAL1 is critical for chondrogenesis and endochondral ossification in MCC.
  • BMAL1 regulates MCC development via the hedgehog signaling pathway.
  • These findings offer potential therapeutic strategies for facial dysmorphism.