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RUNX1 的上调有助于骨间充质干细胞在前交叉韧带重建后腱骨愈合。

Upregulation of Runt related transcription factor 1 (RUNX1) contributes to tendon-bone healing after anterior cruciate ligament reconstruction using bone mesenchymal stem cells.

机构信息

The Second Department of Joint Surgery, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051, Hebei, People's Republic of China.

出版信息

J Orthop Surg Res. 2022 May 13;17(1):266. doi: 10.1186/s13018-022-03152-y.

Abstract

BACKGROUND

Anterior cruciate ligament (ACL) injury could lead to functional impairment along with disabilities. ACL reconstruction often fails owing to the regeneration failure of tendon-bone interface. Herein, we aimed to investigate the effects of Runt related transcription factor 1 (RUNX1) on tendon-bone healing after ACL reconstruction using bone mesenchymal stem cells (BMSCs).

METHODS

BMSCs were isolated from the marrow cavity of rat femur, followed by the modification of RUNX1 with lentiviral system. Then, an ACL reconstruction model of rats was established with autografts.

RESULTS

Results of flow cytometry exhibited positive-antigen CD44 and CD90, as well as negative-antigen CD34 and CD45 of the BMSCs. Then, we found that RUNX1-upregulated BMSCs elevated the decreased biomechanical strength of the tendon grafts after ACL reconstruction. Moreover, based on the histological observation, upregulation of RUNX1 was linked with better recovery around the bone tunnel, a tighter tendon-bone interface, and more collagen fibers compared to the group of BMSCs infected with LV-NC. Next, RUNX1-upregulated BMSCs promoted osteogenesis after ACL reconstruction, as evidenced by the mitigation of severe loss and erosion of the cartilage and bone in the tibial and femur area, as well as the increased number of osteoblasts identified by the upregulation of alkaline phosphatase, osteocalcin, and osteopontin in the tendon-bone interface.

CONCLUSION

Elevated expression of RUNX1 contributed to tendon-bone healing after ACL reconstruction using BMSCs.

摘要

背景

前交叉韧带(ACL)损伤可导致功能障碍和残疾。由于肌腱-骨界面的再生失败,ACL 重建往往会失败。在此,我们旨在研究 Runt 相关转录因子 1(RUNX1)对使用骨髓间充质干细胞(BMSCs)进行 ACL 重建后肌腱-骨愈合的影响。

方法

从大鼠股骨骨髓腔分离 BMSCs,然后用慢病毒系统修饰 RUNX1。然后,用自体移植物建立大鼠 ACL 重建模型。

结果

流式细胞术结果显示 BMSCs 呈阳性抗原 CD44 和 CD90,呈阴性抗原 CD34 和 CD45。然后,我们发现 RUNX1 上调的 BMSCs 提高了 ACL 重建后肌腱移植物生物力学强度的降低。此外,基于组织学观察,与 LV-NC 感染组相比,RUNX1 上调与骨隧道周围更好的恢复、更紧密的肌腱-骨界面以及更多的胶原纤维有关。接下来,RUNX1 上调的 BMSCs 促进 ACL 重建后的成骨作用,表现为胫骨和股骨区域软骨和骨的严重丢失和侵蚀减轻,以及肌腱-骨界面中碱性磷酸酶、骨钙素和骨桥蛋白上调所识别的成骨细胞数量增加。

结论

RUNX1 的表达升高有助于 BMSCs 进行 ACL 重建后的肌腱-骨愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02fd/9107123/330f3b73aa8e/13018_2022_3152_Fig1_HTML.jpg

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