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A PTHrP Gradient Drives Mandibular Condylar Chondrogenesis via Runx2.

C Tsutsumi-Arai1, Y Arai1, A Tran1

  • 1University of Texas Health Science Center at Houston School of Dentistry, Houston, TX, USA.

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|December 7, 2023
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Summary

Parathyroid hormone-related protein (PTHrP) from superficial cells in mandibular condylar cartilage promotes chondrocyte proliferation and prevents premature differentiation by maintaining Runx2 expression, ensuring proper jaw growth.

Keywords:
articular cartilagebone developmentchondrocytesmandibular condylar cartilage (MCC)periosteumtemporomandibular joint

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Area of Science:

  • Developmental Biology
  • Skeletal Biology
  • Cell Biology

Background:

  • Mandibular condylar cartilage (MCC) is crucial for vertical mandibular growth via endochondral ossification.
  • Parathyroid hormone-related protein (PTHrP) regulates chondrogenesis in long bones, but its role in MCC is unclear.
  • Understanding PTHrP's function in MCC is vital for comprehending temporomandibular joint development.

Purpose of the Study:

  • To map PTHrP-expressing cells in the postnatal MCC.
  • To define the functional role of PTHrP in mandibular condyle development.
  • To elucidate the mechanism by which PTHrP regulates chondrogenesis in the MCC.

Main Methods:

  • Utilized a Pthrp-mCherry knock-in reporter mouse strain to visualize PTHrP localization.
  • Analyzed Pthrp knockout (PTHrP-KO) mice to assess the function of PTHrP.
  • Examined chondrocyte proliferation, differentiation markers (SOX9, Col10a1), and gene expression (Runx2, Sp7) at various embryonic stages.

Main Results:

  • PTHrP is expressed in the superficial layer of the MCC, acting on adjacent polymorphic layer cells.
  • PTHrP-KO mice exhibited truncated mandibular condyles, reduced cell proliferation, and loss of SOX9+ chondrocytes.
  • PTHrP deficiency led to transient hypertrophic chondrocytes followed by their loss, indicating premature chondrocyte exhaustion. Runx2 expression was significantly reduced in PTHrP-KO MCC.

Conclusions:

  • Superficial layer-derived PTHrP promotes chondrocyte precursor proliferation and prevents premature differentiation in the MCC.
  • PTHrP maintains Runx2 expression in the polymorphic layer, a key mechanism for MCC development.
  • This study reveals a unique PTHrP gradient-directed mechanism regulating mandibular condylar cartilage chondrogenesis.