Characterization of dental pulp stem cells isolated from a patient diagnosed with Crouzon syndrome.
Characterization of dental pulp stem cells isolated from a patient diagnosed with Crouzon syndrome.
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DOI：
10.1002/jcp.30241
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发表时间：
2021-07
影响因子：
5.6
通讯作者：
Tsutsui TW
中科院分区：
文献类型：
--
作者：
Torii D;Kobayashi T;Horie T;Tsutsui TW
从罕见疾病患者中分离的干细胞对于阐明其病因和实现再生治疗的机制非常重要。然而，使用患者来源的牙髓干细胞(DPSCS)进行组织再生的机制尚不清楚。在本研究中，我们研究了具有Gly338Arg成纤维细胞生长因子受体2突变的Crouzon综合征患者来源的DPSCS(CS-DPSCS)中与细胞分化相关的mRNA和蛋白的表达水平。健康供者DPSCs和CS-DPSCs的多能性相关基因表达水平相同。CS-DPSCs的骨钙素(OCN)表达高于健康供者DPSCs。与未处理的对照细胞相比，CS-DPSCs在佛波酯(PMA)处理的细胞中OCN的表达增加幅度低于健康供者DPSCs。与未处理的对照细胞相比，CS-DPSCs在PMA处理的细胞中p38和p44/42的磷酸化率低于健康供体DPSCs。这些结果表明，CS-DPSCs比健康供体DPSCs具有更高的OCN表达和更低的PMA刺激反应性。我们检测了佛波酯对Crouzon综合征患者牙髓干细胞(CS-DPSCS)成牙本质细胞分化的分子机制，以分析CS-DPSCS中成纤维细胞生长因子的信号转导和骨钙素的表达。
Stem cells isolated from patients with rare diseases are important to elucidate their pathogeny and mechanisms to enable regenerative therapy. However, the mechanisms underlying tissue regeneration using patient‐derived dental pulp stem cells (DPSCs) are unclear. In this study, we investigated the levels of mRNA and protein expression related to cellular differentiation of Crouzon syndrome patient‐derived DPSCs (CS‐DPSCs) with a Gly338Arg fibroblast growth factor receptor 2 mutation. Multipotency‐related gene expression levels were equivalent in both healthy donor DPSCs and CS‐DPSCs. CS‐DPSCs showed higher osteocalcin (OCN) expression than healthy donor DPSCs. CS‐DPSCs showed a lower increase in the rate of OCN expression among phorbol 12‐myristate 13‐acetate (PMA)‐treated cells than healthy donor DPSCs compared with untreated control cells. CS‐DPSCs showed a lower phosphorylation rate of p38 and p44/42 in PMA‐treated cells than healthy donor DPSCs compared with untreated control cells. These results demonstrate that CS‐DPSCs have higher OCN expression and lower PMA stimulation‐responsiveness than healthy donor DPSCs. We examined the cellular response to phorbol 12‐myristate 13‐acetate stimulation to elucidate the molecular mechanisms of odontoblastic differentiation in dental pulp stem cells derived from a Crouzon syndrome patient (CS‐DPSCs) for analyzing FGF signal transduction and osteocalcin expression in CS‐DPSCs.
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