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The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells.
Wang, Yiyun; Qin, Qizhi; Wang, Ziyi; Negri, Stefano; Sono, Takashi; Tower, Robert J; Li, Zhao; Xing, Xin; Archer, Mary; Thottappillil, Neelima; Zhu, Manyu; Suarez, Allister; Kim, Deok-Ho; Harvey, Tyler; Fan, Chen-Ming; James, Aaron W.
Affiliation
  • Wang Y; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Qin Q; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Wang Z; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Negri S; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Sono T; Orthopaedic and Trauma Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology of the University of Verona, 37134, Verona, Italy.
  • Tower RJ; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Li Z; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Xing X; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Archer M; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Thottappillil N; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Zhu M; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Suarez A; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Kim DH; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Harvey T; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Fan CM; Department of Embryology, Carnegie Institution of Washington, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • James AW; Department of Embryology, Carnegie Institution of Washington, Johns Hopkins University, Baltimore, MD, 21218, USA.
Cell Death Dis ; 15(6): 420, 2024 Jun 17.
Article in En | MEDLINE | ID: mdl-38886383
ABSTRACT
The regeneration of the mammalian skeleton's craniofacial bones necessitates the action of intrinsic and extrinsic inductive factors from multiple cell types, which function hierarchically and temporally to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse calvarial suture recently identified a suture mesenchymal progenitor population with previously unappreciated tendon- or ligament-associated gene expression profile. Here, we developed a Mohawk homeobox (MkxCG; R26RtdT) reporter mouse and demonstrated that this reporter identifies an adult calvarial suture resident cell population that gives rise to calvarial osteoblasts and osteocytes during homeostatic conditions. Single-cell RNA sequencing (scRNA-Seq) data reveal that Mkx+ suture cells display a progenitor-like phenotype with expression of teno-ligamentous genes. Bone injury with Mkx+ cell ablation showed delayed bone healing. Remarkably, Mkx gene played a critical role as an osteo-inhibitory factor in calvarial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Localized deletion of Mkx in vivo also resulted in robustly increased calvarial defect repair. We further showed that mechanical stretch dynamically regulates Mkx expression, in turn regulating calvarial cell osteogenesis. Together, we define Mkx+ cells within the suture mesenchyme as a progenitor population for adult craniofacial bone repair, and Mkx acts as a mechanoresponsive gene to prevent osteogenic differentiation within the stem cell niche.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Skull / Cell Differentiation / Homeodomain Proteins Limits: Animals Language: En Journal: Cell Death Dis Year: 2024 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Skull / Cell Differentiation / Homeodomain Proteins Limits: Animals Language: En Journal: Cell Death Dis Year: 2024 Document type: Article Affiliation country: United States
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