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髓系来源的抑制性细胞在骨愈合过程从反应期向修复期过渡中的潜在作用。

Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process.

机构信息

Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan.

出版信息

Int J Med Sci. 2021 Feb 19;18(8):1824-1830. doi: 10.7150/ijms.51946. eCollection 2021.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive functions; these cells play a key role in infection, immunization, chronic inflammation, and cancer. Recent studies have reported that immunosuppression plays an important role in the healing process of tissues and that Treg play an important role in fracture healing. MDSCs suppress active T cell proliferation and reduce the severity of arthritis in mice and humans. Together, these findings suggest that MDSCs play a role in bone biotransformation. In the present study, we examined the role of MDSCs in the bone healing process by creating a bone injury at the tibial epiphysis in mice. MDSCs were identified by CD11b and GR1 immunohistochemistry and their role in new bone formation was observed by detection of Runx2 and osteocalcin expression. Significant numbers of MDSCs were observed in transitional areas from the reactionary to repair stages. Interestingly, MDSCs exhibited Runx2 and osteocalcin expression in the transitional area but not in the reactionary area. And at the same area, cllagene-1 and ALP expression level increased in osteoblast progenitor cells. These data is suggesting that MDSCs emerge to suppress inflammation and support new bone formation. Here, we report, for the first time (to our knowledge), the role of MDSCs in the initiation of bone formation. MDSC appeared at the transition from inflammation to bone making and regulates bone healing by suppressing inflammation.

摘要

髓系来源的抑制性细胞(MDSCs)是一群具有免疫抑制功能的不成熟髓系细胞的异质性群体;这些细胞在感染、免疫、慢性炎症和癌症中发挥关键作用。最近的研究报告称,免疫抑制在组织的愈合过程中起着重要作用,而 Treg 在骨折愈合中起着重要作用。MDSCs 抑制活性 T 细胞增殖,并降低小鼠和人类关节炎的严重程度。这些发现共同表明 MDSCs 在骨转化中发挥作用。在本研究中,我们通过在小鼠胫骨骨骺处造成骨损伤来研究 MDSCs 在骨愈合过程中的作用。通过 CD11b 和 GR1 免疫组织化学鉴定 MDSCs,并通过检测 Runx2 和骨钙素表达观察其在新骨形成中的作用。在从反应期到修复期的过渡区观察到大量 MDSCs。有趣的是,MDSCs 在过渡区表达 Runx2 和骨钙素,但在反应区不表达。并且在同一区域,成骨细胞祖细胞中的胶原酶-1 和 ALP 表达水平增加。这些数据表明 MDSCs 出现以抑制炎症并支持新骨形成。在这里,我们首次(据我们所知)报告了 MDSCs 在骨形成启动中的作用。MDSC 出现在炎症向成骨转化的过程中,并通过抑制炎症来调节骨愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c44/7976590/a754c76f146e/ijmsv18p1824g001.jpg

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