Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China.
Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Stem Cell Res Ther. 2021 Feb 25;12(1):148. doi: 10.1186/s13287-021-02220-0.
During orthodontic tooth movement (OTM), alveolar bone remodelling is closely related to mechanical force. It is unclear whether stem cells can affect osteoclastogenesis to promote OTM. This study aimed to investigate the role of mouse bone marrow mesenchymal stem cells (mBMMSCs) under compression load in OTM.
A mouse OTM model was established, and GFP-labelled mBMMSCs and normal saline were injected into different groups of mice by tail vein injection. OTM distance was measured using tissue specimens and micro-computed tomography (micro-CT). The locations of mBMMSCs were traced using GFP immunohistochemistry. Haematoxylin-eosin staining, tartrate-resistant acid phosphate (TRAP) staining and immunohistochemistry of Runx2 and lipoprotein lipase were used to assess changes in the periodontal ligament during OTM. mBMMSCs under compression were co-cultured with mouse bone marrow-derived macrophages (mBMMs), and the gene expression levels of Rankl, Mmp-9, TRAP, Ctsk, Alp, Runx2, Ocn and Osterix were determined by RT-PCR.
Ten days after mBMMSCs were injected into the tail vein of mice, the OTM distance increased from 176 (normal saline) to 298.4 μm, as determined by tissue specimen observation, and 174.2 to 302.6 μm, as determined by micro-CT metrological analysis. GFP-labelled mBMMSCs were mostly located on the compressed side of the periodontal ligament. Compared to the saline group, the number of osteoclasts in the alveolar bone increased significantly (P < 0.01) on the compressed side in the mBMMSC group. Three days after mBMMSC injection, the number of Runx2-GFP double-positive cells on the tension side was significantly higher than that on the compression side. After applying compressive force on the mBMMSCs in vitro for 2 days, RANKL expression was significantly higher than in the non-compression cells, but expression of Alp, Runx2, Ocn and Osterix was significantly decreased (P < 0.05). The numbers of osteoclasts differentiated in response to mBMMs co-cultured with mBMMSCs under pressure load and expression of osteoclast differentiation marker genes (Mmp-9, TRAP and Ctsk) were significantly higher than those in mBMMs stimulated by M-CSF alone (P < 0.05).
mBMMSCs are not only recruited to the compressed side of the periodontal ligament but can also promote osteoclastogenesis by expressing Rankl, improving the efficiency of OTM.
在正畸牙齿移动（OTM）过程中，牙槽骨重塑与机械力密切相关。目前尚不清楚干细胞是否可以影响破骨细胞生成以促进 OTM。本研究旨在探讨在压缩负荷下小鼠骨髓间充质干细胞（mBMMSCs）在 OTM 中的作用。
建立了小鼠 OTM 模型，并通过尾静脉注射将 GFP 标记的 mBMMSCs 和生理盐水注入不同组别的小鼠。使用组织标本和微计算机断层扫描（micro-CT）测量 OTM 距离。使用 GFP 免疫组织化学追踪 mBMMSCs 的位置。通过苏木精-伊红染色、抗酒石酸酸性磷酸酶（TRAP）染色以及 Runx2 和脂蛋白脂肪酶的免疫组织化学染色，评估 OTM 过程中牙周韧带的变化。将 mBMMSCs 进行压缩培养后与小鼠骨髓来源的巨噬细胞（mBMMs）共培养，通过 RT-PCR 测定 Rankl、Mmp-9、TRAP、Ctsk、Alp、Runx2、Ocn 和 Osterix 的基因表达水平。
在将 mBMMSCs 注入小鼠尾静脉 10 天后，通过组织标本观察，OTM 距离从生理盐水组的 176μm 增加到 298.4μm，通过 micro-CT 计量分析增加到 174.2μm 至 302.6μm。GFP 标记的 mBMMSCs 主要位于牙周韧带的受压侧。与生理盐水组相比，mBMMSC 组牙槽骨中的破骨细胞数量明显增加（P<0.01）。在 mBMMSC 注射后 3 天，张力侧的 Runx2-GFP 双阳性细胞数量明显高于压缩侧。在体外对 mBMMSCs 施加 2 天的压缩力后，RANKL 的表达明显高于非压缩细胞，但 Alp、Runx2、Ocn 和 Osterix 的表达明显降低（P<0.05）。在压力负荷下与 mBMMs 共培养的 mBMMSCs 分化的破骨细胞数量以及破骨细胞分化标记基因（Mmp-9、TRAP 和 Ctsk）的表达均明显高于单独用 M-CSF 刺激的 mBMMs（P<0.05）。
mBMMSCs 不仅募集到牙周韧带的受压侧，而且通过表达 Rankl 促进破骨细胞生成，提高 OTM 的效率。
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