Transplantation of mesenchymal stem cells ameliorates secondary osteoporosis through interleukin-17-impaired functions of recipient bone marrow mesenchymal stem cells in MRL/lpr mice.
Transplantation of mesenchymal stem cells ameliorates secondary osteoporosis through interleukin-17-impaired functions of recipient bone marrow mesenchymal stem cells in MRL/lpr mice.
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DOI：
10.1186/s13287-015-0091-4
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发表时间：
2015-05-27
影响因子：
7.5
通讯作者：
Yamaza T
中科院分区：
文献类型：
--
作者：
Ma L;Aijima R;Hoshino Y;Yamaza H;Tomoda E;Tanaka Y;Sonoda S;Song G;Zhao W;Nonaka K;Shi S;Yamaza T
继发性骨质疏松症在系统性红斑狼疮中很常见，并由于脆性骨折导致生活质量下降，即使在原发疾病有所改善的患者中也是如此。系统性骨髓间充质干细胞移植可以改善MRL/LPR小鼠系统性红斑狼疮模型的骨丢失和自身免疫紊乱，但骨再生的详细治疗机制尚不完全清楚。本研究将人骨髓间充质干细胞和脱落牙干细胞移植到MRL/LPR小鼠体内，探讨其治疗系统性红斑狼疮模型小鼠继发性骨质疏松性疾病的作用机制。通过体内、外系统人间充质干细胞移植对MRL/LPR小鼠骨丢失的影响进行分析。在系统人骨髓间充质干细胞移植后，从干性、成骨和破骨三个方面评价MRL/LPR小鼠受体BMMSC的功能，并在成骨和破骨诱导下进行一系列共培养实验，以检测IL-17损伤的受体BMMSCs在MRL/LPR小鼠骨髓中的作用。系统移植人BMMSCs和SHAD可恢复MRL/LPR小鼠骨密度和结构的减少。为探讨其机制，我们发现受者受损的BMMSCs通过促进破骨细胞生成和抑制成骨细胞生成来介导MRL/LPR小鼠继发性骨质疏松症的骨代谢负性转换。此外，MRL/LPR小鼠受体骨髓中依赖IL-17的高免疫状态损伤了受体BMMSCs，从而抑制了成骨细胞的能力，促进了破骨细胞的诱导。为了克服骨代谢的异常，系统移植人BMMSCs并植入MRL/LPR小鼠体内，通过抑制受体骨髓中的IL-17来改善功能受损的受体BMMSCs，然后通过成骨细胞和破骨细胞的平衡来维持正常的正向骨代谢。提示IL-17和受体BMMSCs可能是系统性红斑狼疮继发性骨质疏松症的治疗靶点。本文的在线版本(doi：10.1186/s13287-0150091-4)包含补充材料，授权用户可以使用。
Secondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice. The effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice. Systemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts. These findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus. The online version of this article (doi:10.1186/s13287-015-0091-4) contains supplementary material, which is available to authorized users.
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影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
3.7
作者：
Ma L;Makino Y;Yamaza H;Akiyama K;Hoshino Y;Song G;Kukita T;Nonaka K;Shi S;Yamaza T
通讯作者：
Yamaza T
影响因子：
168.9
作者：
Baeten, Dominique;Baraliakos, Xenofon;Hueber, Wolfgang
通讯作者：
Hueber, Wolfgang
影响因子：
4
作者：
Jacobs, J.;Korswagen, L. -A.;Bultink, I. E. M.
通讯作者：
Bultink, I. E. M.
影响因子：
4.4
作者：
Ghannam, Soufiane;Pene, Jerome;Yssel, Hans
通讯作者：
Yssel, Hans