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八钙磷酸盐调节成骨细胞中的多种增殖信号通路。

Multiple proliferation signaling pathways are modulated by octacalcium phosphate in osteoblasts.

机构信息

Dental biomaterials science, School of dentistry and dental research institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

HudensBio Co., Ltd, 318 Cheomdanyeonsin-ro, Buk-gu, Gwangju 61088, Republic of Korea.

出版信息

Int J Med Sci. 2022 Sep 25;19(12):1724-1731. doi: 10.7150/ijms.77017. eCollection 2022.

DOI:10.7150/ijms.77017
PMID:36313230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9608048/
Abstract

Octacalcium phosphate (OCP), a type of bioactive ceramics, may be associated with dentine, tooth apatite, and especially bone generation, and promotes wound healing after fracture. Recently, commercial bone grafting products containing a large amount of OCP material have been released because OCP can be synthesized in large quantities. It is reported to increase cell proliferation, but the interaction between OCP and cell signaling pathways is still unclear. In this study, first, we demonstrated OCP mediated cell signaling pathways with only purified OCP materials. OCP regulated P38, JNK (c-Jun N-terminal kinase), Src, and AKT (protein kinase B) signaling pathways. OCP crystals appeared in the characteristic ribbon shape but varied by several tens of micrometers in size. The X-ray diffraction pattern was the same as previously reported. We studied two concentrations of OCP (10 mg/ml and 20 mg/ml) to understand whether the effect of OCP on cell signaling pathways is dose dependent. We confirmed that OCP treatment affected cell proliferation and alkaline phosphatase and disrupted Src phosphorylation but did not change the total protein level. P38 phosphorylation was activated with OCP treatment and inhibited by SB203580, but P38 total protein level did not change. OCP inhibited JNK phosphorylation signaling, whereas PD98509 inhibited JNK phosphorylation with or without OCP. Interestingly, the AKT total level decreased after OCP treatment, but AKT phosphorylation increased considerably. Our results demonstrate that OCP materials modulate cell signaling pathways and increase cell proliferation.

摘要

八钙磷(OCP)是一种生物活性陶瓷,可能与牙本质、牙磷灰石有关,尤其是与骨骼生成有关,并能促进骨折后的伤口愈合。最近,由于可以大量合成 OCP,含有大量 OCP 材料的商业骨移植产品已经问世。据报道,OCP 能促进细胞增殖,但 OCP 与细胞信号通路的相互作用仍不清楚。在本研究中,我们首先用仅纯化的 OCP 材料证明了 OCP 介导的细胞信号通路。OCP 调节 P38、JNK(c-Jun N-末端激酶)、Src 和 AKT(蛋白激酶 B)信号通路。OCP 晶体呈特征的带状,但大小相差几十微米。X 射线衍射图谱与之前报道的相同。我们研究了两种浓度的 OCP(10mg/ml 和 20mg/ml),以了解 OCP 对细胞信号通路的影响是否具有剂量依赖性。我们证实 OCP 处理影响细胞增殖和碱性磷酸酶,并破坏 Src 磷酸化,但不改变总蛋白水平。OCP 处理激活 P38 磷酸化,并被 SB203580 抑制,但 P38 总蛋白水平没有变化。OCP 抑制 JNK 磷酸化信号,而 PD98509 抑制 JNK 磷酸化,无论是否存在 OCP。有趣的是,OCP 处理后 AKT 总水平下降,但 AKT 磷酸化显著增加。我们的结果表明,OCP 材料调节细胞信号通路并增加细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/e9db16a02d1a/ijmsv19p1724g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/1d76ad98a7f0/ijmsv19p1724g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/5f5ce0b72b97/ijmsv19p1724g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/fd02ef2023db/ijmsv19p1724g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/e9db16a02d1a/ijmsv19p1724g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/1d76ad98a7f0/ijmsv19p1724g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/7dea3a3e3d40/ijmsv19p1724g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/af98b575accc/ijmsv19p1724g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/5f5ce0b72b97/ijmsv19p1724g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/fd02ef2023db/ijmsv19p1724g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498b/9608048/e9db16a02d1a/ijmsv19p1724g006.jpg

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