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与长骨来源的间充质干细胞相比,口腔颌面骨来源的间充质干细胞在增殖和成骨分化方面对 CKIP-1 的敏感性更高。

Superior CKIP-1 sensitivity of orofacial bone-derived mesenchymal stem cells in proliferation and osteogenic differentiation compared to long bone-derived mesenchymal stem cells.

机构信息

School of Stomatology of Qingdao University, Qingdao, Shandong 266003, P.R. China.

State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Mol Med Rep. 2020 Aug;22(2):1169-1178. doi: 10.3892/mmr.2020.11239. Epub 2020 Jun 15.

Abstract

Maxillofacial bone defects caused by multiple factors, including congenital deformations and tumors, have become a research focus in the field of oral medicine. Bone tissue engineering is increasingly regarded as a potential approach for maxillofacial bone repair. Mesenchymal stem cells (MSCs) with different origins display various biological characteristics. The aim of the present study was to investigate the effects of casein kinase‑2 interaction protein‑1 (CKIP‑1) on MSCs, including femoral bone marrow‑derived MSCs (BMMSCs) and orofacial bone‑derived MSCs (OMSCs), isolated from the femoral and orofacial bones of wild‑type (WT) and CKIP‑1 knockout (KO) mice. MSCs were isolated using collagenase II and the main biological characteristics, including proliferation, apoptosis and osteogenic differentiation, were investigated. Subcutaneous transplantation of MSCs in mice was also performed to assess ectopic bone formation. MTT and clone formation assay results indicated that cell proliferation in the KO group was increased compared with the WT group, and OMSCs exhibited significantly increased levels of proliferation compared with BMMSCs. However, the proportion of apoptotic cells was not significantly different between CKIP‑1 KO OMSCs and BMMSCs. Furthermore, it was revealed that osteogenic differentiation was increased in CKIP‑1 KO MSCs compared with WT MSCs, particularly in OMSCs. Consistent with the in vitro results, enhanced ectopic bone formation was observed in CKIP‑1 KO mice compared with WT mice, particularly in OMSCs compared with BMMSCs. In conclusion, the present results indicated that OMSCs may have a superior sensitivity to CKIP‑1 in promoting osteogenesis compared with BMMSCs; therefore, CKIP‑1 KO in OMSCs may serve as an efficient strategy for maxillofacial bone repair.

摘要

多种因素引起的颌面部骨缺损,包括先天性畸形和肿瘤,已成为口腔医学领域的研究热点。骨组织工程越来越被认为是颌骨修复的一种有潜力的方法。不同来源的间充质干细胞(MSCs)具有不同的生物学特性。本研究旨在探讨酪蛋白激酶-2 相互作用蛋白-1(CKIP-1)对来源于股骨和颌面部骨的骨髓间充质干细胞(BMMSCs)和颌面部骨源性间充质干细胞(OMSCs)的影响,这些细胞来自野生型(WT)和 CKIP-1 敲除(KO)小鼠。采用胶原酶 II 分离 MSCs,研究其主要生物学特性,包括增殖、凋亡和成骨分化。还进行了 MSC 皮下移植实验以评估异位骨形成。MTT 和克隆形成实验结果表明,与 WT 组相比,KO 组细胞增殖增加,而 OMSCs 的增殖水平明显高于 BMMSCs。然而,CKIP-1 KO OMSCs 和 BMMSCs 之间凋亡细胞的比例没有显著差异。此外,结果表明 CKIP-1 KO MSC 的成骨分化较 WT MSC 增加,尤其是 OMSCs。与体外结果一致,与 WT 小鼠相比,CKIP-1 KO 小鼠的异位骨形成增强,尤其是 OMSCs 与 BMMSCs 相比。综上所述,这些结果表明,与 BMMSCs 相比,OMSCs 可能对 CKIP-1 促进成骨作用具有更高的敏感性;因此,OMSCs 中的 CKIP-1 KO 可能是颌骨修复的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13aa/7339610/815455cb92e7/MMR-22-02-1169-g00.jpg

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