Indirect osteoblast differentiation by liposomal clodronate.
Indirect osteoblast differentiation by liposomal clodronate.
复制标题
脂质体氯膦酸盐间接成骨细胞分化。
DOI：
10.1111/jcmm.13366
复制
发表时间：
2018-03
影响因子：
5.3
通讯作者：
Kuroda S
中科院分区：
文献类型：
--
作者：
Okada E;Nakata H;Yamamoto M;Kasugai S;Kuroda S
双膦酸盐损害破骨细胞功能，阻碍骨吸收，其机制已被广泛研究。然而，双膦酸盐对成骨细胞成软骨分化和钙沉积的可能影响直到最近才得到证实。此外，来自单核细胞谱系的细胞能够刺激成骨细胞增殖。因此，成骨细胞对各种因素的易感性有待进一步研究。用氯膦酸脂质体（0.1、0.5或1.0 mg/ml）或氯膦酸脂质体的条件培养基处理骨髓源基质细胞的原代培养。将氯膦酸脂质体（0.25 mg）注入小鼠股骨进行体内实验。通过碱性磷酸酶染色和/或活性测定检测氯膦酸脂质体的作用，并采用实时RT - PCR技术研究其对成骨基因表达的影响。骨髓源间充质细胞培养中给予氯膦酸脂质体可增强碱性磷酸酶活性和Runx2和Dlx5 mRNA水平。此外，由氯膦酸脂质体组成的条件培养基也刺激了与体外观察到的相似的成骨特性，并且当用氯膦酸脂质体预处理时，条件培养基中的外泌体数量最多。Western blot分析显示，从氯膦酸脂质体条件培养基中收集的外泌体中存在RANK蛋白。在体内也得到了相同的观察结果，氯膦酸脂质体注射小鼠股骨显示碱性磷酸酶活性和Runx2和Dlx5 mRNA表达增加，尽管单核细胞和巨噬细胞数量减少。综上所述，在氯膦酸盐的作用下，可溶性含RANK外泌体促进了成骨细胞的分化。
Bisphosphonates impair function of osteoclasts and prevent bone resorption, the mechanism of which has been studied extensively. However, the possible effects of bisphosphonates on chondroblast differentiation and calcium deposition by osteoblasts have only been demonstrated recently. Moreover, cells from monocytic lineage are capable of stimulating osteoblast proliferation. Hence, susceptibility of osteoblasts to various factors requires further investigation. A primary culture of bone marrow‐derived stromal cells was treated with liposomal clodronate (0.1, 0.5, or 1.0 mg/ml) or conditioned medium from liposomal clodronate. Liposomal clodronate (0.25 mg) was injected into mouse femur for in vivo experiments. The effects of liposomal clodronate were examined by alkaline phosphatase staining and/or activity assay, and real‐time RT‐PCR was used for studying the effect on osteogenic gene expression. Administration of liposomal clodronate to bone marrow‐derived mesenchymal stromal cell culture enhanced alkaline phosphatase activity and mRNA levels of Runx2 and Dlx5. In addition, conditioned medium from liposomal clodronate also stimulated osteogenic characteristics similar to those of observed in vitro, and the number of exosomes in the conditioned medium was highest when pre‐treated with liposomal clodronate. Western blot analysis revealed the presence of RANK proteins in exosomes collected from conditioned medium of liposomal clodronate. Identical observations were obtained in vivo, as liposomal clodronate‐injected mouse femur showed increased alkaline phosphatase activity and Runx2 and Dlx5 mRNA expressions, even though the numbers of monocytes and macrophages were reduced. In conclusion, osteoblast differentiation was promoted via soluble RANK‐containing exosomes in response to clodronates.
登录
查看更多内容
影响因子：
12.7
作者：
Chang J;Koh AJ;Roca H;McCauley LK
通讯作者：
McCauley LK
影响因子：
7.7
作者：
Rahman MJ;Regn D;Bashratyan R;Dai YD
通讯作者：
Dai YD
影响因子：
9.7
作者：
Hayden, Rebecca S.;Vollrath, Moritz;Kaplan, David L.
通讯作者：
Kaplan, David L.
影响因子：
4.4
作者：
Lam, Roselind S.;O'Brien-Simpson, Neil M.;Reynolds, Eric C.
通讯作者：
Reynolds, Eric C.
人诱导多能干细胞衍生的间充质干细胞分泌的外泌体通过增强骨质疏松大鼠的血管生成和骨生成来修复严重大小的骨缺损
影响因子：
9.2
作者：
Qi X;Zhang J;Yuan H;Xu Z;Li Q;Niu X;Hu B;Wang Y;Li X
通讯作者：
Li X