Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration.

Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration.
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DOI:
10.1016/j.stemcr.2017.03.002
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发表时间:
2017-04-11
期刊:
影响因子:
5.9
通讯作者:
Intini G
Intini G
中科院分区:
医学1区
文献类型:
--
作者:
Wilk K;Yeh SA;Mortensen LJ;Ghaffarigarakani S;Lombardo CM;Bassir SH;Aldawood ZA;Lin CP;Intini G

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出生后的骨骼干细胞表达PRX1(pnPRX1+)已被确定在头盖骨和中轴骨骼。在这里,我们的特点的位置和功能能力的颅骨pnPRX1+细胞。我们发现,pnPRX1+只驻留在颅缝龛,并随着年龄的增长而减少。它们不同于缝线的前成骨细胞和成骨细胞,通过分化成成骨细胞在体外和体内响应WNT信号传导,并且在异位移植时能够再生骨。白喉毒素A(DTA)介导的pnPRX1+细胞的谱系消融和缝切除术干扰了颅骨缺损的再生,并证实了缝线的pnPRX1+细胞是骨再生所需的。将具有可追踪的pnPRX1+细胞的缝线原位移植到野生型动物中表明,缝线的pnPRX1+细胞有助于颅骨骨缺损再生。然而,DTA介导的pnPRX1+谱系消融不会干扰颅骨发育。颅骨缝是表达PRX 1的细胞的唯一生态位颅骨的出生后PRX 1表达细胞是骨再生所必需的颅骨的出生后PRX 1表达细胞是发育所必需的Lin,Intini和同事通过活体显微镜,谱系追踪和谱系消融实验确定颅骨缝是表达PRX 1的出生后骨骼干细胞的干细胞生态位。他们表明,颅骨的PRX1表达细胞是骨再生所需的,但对于颅骨发育是不可或缺的。
Post-natal skeletal stem cells expressing PRX1 (pnPRX1+) have been identified in the calvaria and in the axial skeleton. Here we characterize the location and functional capacity of the calvarial pnPRX1+ cells. We found that pnPRX1+ reside exclusively in the calvarial suture niche and decrease in number with age. They are distinct from preosteoblasts and osteoblasts of the sutures, respond to WNT signaling in vitro and in vivo by differentiating into osteoblasts, and, upon heterotopic transplantation, are able to regenerate bone. Diphtheria toxin A (DTA)-mediated lineage ablation of pnPRX1+ cells and suturectomy perturb regeneration of calvarial bone defects and confirm that pnPRX1+ cells of the sutures are required for bone regeneration. Orthotopic transplantation of sutures with traceable pnPRX1+ cells into wild-type animals shows that pnPRX1+ cells of the suture contribute to calvarial bone defect regeneration. DTA-mediated lineage ablation of pnPRX1+ does not, however, interfere with calvarial development. The suture is the exclusive niche of the calvarial PRX1-expressing cells Postnatal PRX1-expressing cells of the calvaria are required for bone regeneration Postnatal Prx1-expressing cells of the calvaria are dispensable for development Lin, Intini, and colleagues identify the calvarial suture as the stem cell niche for PRX1-expressing postnatal skeletal stem cells by means of intravital microscopy, lineage-tracing, and lineage-ablation experiments. They show that PRX1-expressing cells of the calvaria are required for bone regeneration but are dispensable for calvarial development.