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The suture provides a niche for mesenchymal stem cells of craniofacial bones.

Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y - Nat. Cell Biol. (2015)

Bottom Line: Gli1+ cells are typical MSCs in vitro.Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population.Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103 Los Angeles, California 90033, USA.

ABSTRACT
Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.

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Gli1+ cells are restricted to the suture mesenchyme of craniofacial bones and are undifferentiated cells. (a-f) Whole mount LacZ staining (blue) of calvarial bones of newborn (P0), 7, 14 and 21 day old (P7, P14, P21) and one- and three-month-old Gli1-LacZ mice. (g-i) LacZ staining of sections of sagittal sutures and parietal bones of P0, P7 and P14 mice indicates Gli1+ cells are present in the suture mesenchyme (asterisks), periosteum (arrows) and dura (arrowheads). (j-l) LacZ staining of sections of the sagittal suture of one-month-old Gli1-LacZ mice. Asterisk indicates exclusive Gli1 expression within the suture mesenchyme. No positive staining is detectable in the periosteum (white arrow) and dura (white arrowhead). Boxed areas in j are displayed in k and l. (m-p) LacZ staining of the mid-suture mesenchyme in the coronal (m), interpalatal (n), presphenoid-palatal (o) and maxilla-palatal (p) sutures of one-month-old Gli1-LacZ mice. (q-t) ALPase (blue) and immunohistochemical (red) staining of sagittal sutures of one-month-old mice. Osteogenic markers including ALPase (q), Sp7 (r), osteocalcin(OC) (s) and Runx2 (t) are not detectable in the suture mesenchyme (asterisks). The periosteum (arrows) and dura (arrowheads) strongly express these markers. Boxed areas in r and t are enlarged in panels r’ and t’, respectively, showing positive expression in the osteogenic fronts (arrowheads). Dotted lines outline margins of craniofacial bones. Scale bars in panels a-f, 1mm; other scale bars, 100 μm.
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Figure 1: Gli1+ cells are restricted to the suture mesenchyme of craniofacial bones and are undifferentiated cells. (a-f) Whole mount LacZ staining (blue) of calvarial bones of newborn (P0), 7, 14 and 21 day old (P7, P14, P21) and one- and three-month-old Gli1-LacZ mice. (g-i) LacZ staining of sections of sagittal sutures and parietal bones of P0, P7 and P14 mice indicates Gli1+ cells are present in the suture mesenchyme (asterisks), periosteum (arrows) and dura (arrowheads). (j-l) LacZ staining of sections of the sagittal suture of one-month-old Gli1-LacZ mice. Asterisk indicates exclusive Gli1 expression within the suture mesenchyme. No positive staining is detectable in the periosteum (white arrow) and dura (white arrowhead). Boxed areas in j are displayed in k and l. (m-p) LacZ staining of the mid-suture mesenchyme in the coronal (m), interpalatal (n), presphenoid-palatal (o) and maxilla-palatal (p) sutures of one-month-old Gli1-LacZ mice. (q-t) ALPase (blue) and immunohistochemical (red) staining of sagittal sutures of one-month-old mice. Osteogenic markers including ALPase (q), Sp7 (r), osteocalcin(OC) (s) and Runx2 (t) are not detectable in the suture mesenchyme (asterisks). The periosteum (arrows) and dura (arrowheads) strongly express these markers. Boxed areas in r and t are enlarged in panels r’ and t’, respectively, showing positive expression in the osteogenic fronts (arrowheads). Dotted lines outline margins of craniofacial bones. Scale bars in panels a-f, 1mm; other scale bars, 100 μm.

Mentions: We hypothesized that Gli1+ cells are MSCs for craniofacial bones, as they are for the incisor mesenchyme26. First, we investigated the expression of Gli1 in mouse calvarial bones. At postnatal day 0 (P0), Gli1+ cells are detectable throughout the entire periosteum, dura and suture mesenchyme, but not in the fontanelles or osteocytes (Figure 1a, g). A similar distribution pattern was detectable at P7 and P14 (Figure 1b-c, h-i). Between P21 and 1 month postnatally, Gli1+ cells are gradually restricted to the suture region (Figure 1d-e). At one month of age, Gli1+ cells are only detectable within the suture mesenchyme, mostly in the mid-suture region, but are absent from the periosteum, dura and osteocytes (Figure 1j-l). Such a suture-specific pattern was also detectable in mice at three months of age and older (Figure 1f).


The suture provides a niche for mesenchymal stem cells of craniofacial bones.

Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y - Nat. Cell Biol. (2015)

Gli1+ cells are restricted to the suture mesenchyme of craniofacial bones and are undifferentiated cells. (a-f) Whole mount LacZ staining (blue) of calvarial bones of newborn (P0), 7, 14 and 21 day old (P7, P14, P21) and one- and three-month-old Gli1-LacZ mice. (g-i) LacZ staining of sections of sagittal sutures and parietal bones of P0, P7 and P14 mice indicates Gli1+ cells are present in the suture mesenchyme (asterisks), periosteum (arrows) and dura (arrowheads). (j-l) LacZ staining of sections of the sagittal suture of one-month-old Gli1-LacZ mice. Asterisk indicates exclusive Gli1 expression within the suture mesenchyme. No positive staining is detectable in the periosteum (white arrow) and dura (white arrowhead). Boxed areas in j are displayed in k and l. (m-p) LacZ staining of the mid-suture mesenchyme in the coronal (m), interpalatal (n), presphenoid-palatal (o) and maxilla-palatal (p) sutures of one-month-old Gli1-LacZ mice. (q-t) ALPase (blue) and immunohistochemical (red) staining of sagittal sutures of one-month-old mice. Osteogenic markers including ALPase (q), Sp7 (r), osteocalcin(OC) (s) and Runx2 (t) are not detectable in the suture mesenchyme (asterisks). The periosteum (arrows) and dura (arrowheads) strongly express these markers. Boxed areas in r and t are enlarged in panels r’ and t’, respectively, showing positive expression in the osteogenic fronts (arrowheads). Dotted lines outline margins of craniofacial bones. Scale bars in panels a-f, 1mm; other scale bars, 100 μm.
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Related In: Results  -  Collection

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Figure 1: Gli1+ cells are restricted to the suture mesenchyme of craniofacial bones and are undifferentiated cells. (a-f) Whole mount LacZ staining (blue) of calvarial bones of newborn (P0), 7, 14 and 21 day old (P7, P14, P21) and one- and three-month-old Gli1-LacZ mice. (g-i) LacZ staining of sections of sagittal sutures and parietal bones of P0, P7 and P14 mice indicates Gli1+ cells are present in the suture mesenchyme (asterisks), periosteum (arrows) and dura (arrowheads). (j-l) LacZ staining of sections of the sagittal suture of one-month-old Gli1-LacZ mice. Asterisk indicates exclusive Gli1 expression within the suture mesenchyme. No positive staining is detectable in the periosteum (white arrow) and dura (white arrowhead). Boxed areas in j are displayed in k and l. (m-p) LacZ staining of the mid-suture mesenchyme in the coronal (m), interpalatal (n), presphenoid-palatal (o) and maxilla-palatal (p) sutures of one-month-old Gli1-LacZ mice. (q-t) ALPase (blue) and immunohistochemical (red) staining of sagittal sutures of one-month-old mice. Osteogenic markers including ALPase (q), Sp7 (r), osteocalcin(OC) (s) and Runx2 (t) are not detectable in the suture mesenchyme (asterisks). The periosteum (arrows) and dura (arrowheads) strongly express these markers. Boxed areas in r and t are enlarged in panels r’ and t’, respectively, showing positive expression in the osteogenic fronts (arrowheads). Dotted lines outline margins of craniofacial bones. Scale bars in panels a-f, 1mm; other scale bars, 100 μm.
Mentions: We hypothesized that Gli1+ cells are MSCs for craniofacial bones, as they are for the incisor mesenchyme26. First, we investigated the expression of Gli1 in mouse calvarial bones. At postnatal day 0 (P0), Gli1+ cells are detectable throughout the entire periosteum, dura and suture mesenchyme, but not in the fontanelles or osteocytes (Figure 1a, g). A similar distribution pattern was detectable at P7 and P14 (Figure 1b-c, h-i). Between P21 and 1 month postnatally, Gli1+ cells are gradually restricted to the suture region (Figure 1d-e). At one month of age, Gli1+ cells are only detectable within the suture mesenchyme, mostly in the mid-suture region, but are absent from the periosteum, dura and osteocytes (Figure 1j-l). Such a suture-specific pattern was also detectable in mice at three months of age and older (Figure 1f).

Bottom Line: Gli1+ cells are typical MSCs in vitro.Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population.Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103 Los Angeles, California 90033, USA.

ABSTRACT
Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.

Show MeSH
Related in: MedlinePlus