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CD10阳性细胞对人上颌/下颌骨髓间充质干细胞成骨分化的影响

Effect of CD10-positive cells on osteogenic differentiation of human maxillary/mandibular bone marrow-derived mesenchymal stem cells.

作者信息

Sakurai Tomoaki, Ishii Masakazu, Miyata Haruka, Ikeda Nao, Suehiro Fumio, Komabashiri Naohiro, Oura Yurika, Nishimura Masahiro

机构信息

Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate school of Medical and Dental Science, Kagoshima 890-8544, Japan.

Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate school of Medical and Dental Science, Kagoshima 890-8544, Japan.

出版信息

Arch Oral Biol. 2025 Feb;170:106135. doi: 10.1016/j.archoralbio.2024.106135. Epub 2024 Nov 23.

Abstract

OBJECTIVE

This study was aimed at investigating the effect of CD10-positive cells within the maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) on osteogenic differentiation of MBMSCs.

DESIGN

CD10 expression in iliac bone marrow-derived MSCs (IBMSCs), MBMSCs, and gingival fibroblasts was measured using flow cytometry. The osteogenic potential of 19 MBMSC lines was evaluated, and based on it, they were classified into osteogenic-High and osteogenic-Low groups. The percentage of CD10-positive cells in each group was compared. Effect of coculturing gingival fibroblasts and CD10-positive cells on the osteogenic potential of MBMSCs was also assessed. Expression of tissue inhibitor of metalloprotease-1 (TIMP-1) in osteogenic-High and osteogenic-Low MBMSCs was measured using quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The molecular mechanisms underlying the regulation of osteogenic differentiation in MBMSCs were investigated.

RESULTS

CD10 was not expressed in IBMSCs, but was highly expressed in fibroblasts. In MBMSCs, the CD10-positivity rate varied considerably between cells. MBMSCs with a high-CD10 positivity rate showed low osteogenic potential. Coculture with fibroblasts or CD10-positive cells reduced the osteogenic potential of MBMSCs. TIMP-1 was highly expressed in CD10-positive cells, and osteogenic-Low MBMSCs showed significantly higher TIMP-1 expression compared with osteogenic-High MBMSCs. β-catenin signaling was suppressed in osteogenic-Low MBMSCs.

CONCLUSION

This study revealed that TIMP-1 secreted from CD10-positive cells may be involved in the suppression of the osteogenic potential of MBMSCs by contamination with CD10-positive cells. This finding provides important insights for developing bone regeneration therapies using MBMSCs.

摘要

目的

本研究旨在探讨上颌/下颌骨髓间充质干细胞(MBMSCs)中CD10阳性细胞对MBMSCs成骨分化的影响。

设计

采用流式细胞术检测髂骨髓间充质干细胞(IBMSCs)、MBMSCs和牙龈成纤维细胞中CD10的表达。评估了19个MBMSC系的成骨潜能,并据此将它们分为成骨高组和成骨低组。比较了每组中CD10阳性细胞的百分比。还评估了牙龈成纤维细胞与CD10阳性细胞共培养对MBMSCs成骨潜能的影响。采用定量实时聚合酶链反应、蛋白质免疫印迹法和酶联免疫吸附测定法检测成骨高和成骨低的MBMSCs中金属蛋白酶组织抑制剂-1(TIMP-1)的表达。研究了MBMSCs成骨分化调控的分子机制。

结果

CD10在IBMSCs中不表达,但在成纤维细胞中高表达。在MBMSCs中,细胞间CD10阳性率差异很大。CD10阳性率高的MBMSCs成骨潜能低。与成纤维细胞或CD10阳性细胞共培养降低了MBMSCs的成骨潜能。TIMP-1在CD10阳性细胞中高表达,与成骨高的MBMSCs相比,成骨低的MBMSCs中TIMP-1表达明显更高。β-连环蛋白信号通路在成骨低的MBMSCs中受到抑制。

结论

本研究表明,CD10阳性细胞分泌的TIMP-1可能通过污染CD10阳性细胞参与抑制MBMSCs的成骨潜能。这一发现为利用MBMSCs开发骨再生疗法提供了重要见解。

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