K562来源的外泌体对骨髓间充质干细胞造血和成骨基因表达的影响

doi:10.3877/cma.j.issn.2095-1221.2021.04.003

目的

探讨K562细胞来源的外泌体（EXO）对骨髓间充质干细胞（BMMSCs）支持造血和成骨分化相关因子表达的影响。

方法

利用超速离心法提取K562细胞培养上清中的EXO并进行鉴定。在体外，诱导BMMSCs的成骨分化，根据是否加入EXO分为3组：BMMSCs+PBS、BMMSCs+EXO （25 μg/mL）、BMMSCs+EXO （50 μg/mL）。qRT-PCR和Western blot检测BMMSCs中支持造血和成骨基因的表达，ELISA测定碱性磷酸酶（ALP）活性和细胞基质钙含量。多时间点间比较采用重复测量方差分析，多组间差异采用ANOVA分析，组间两两比较采用Tukey's test检验。

结果

三组各时间点CXC型趋化因子配体12 （CXCL12）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-6 （IL-6）、Runt相关转录因子2 （RUNX2）、碱性磷酸酶（ALP）和Ⅰ型胶原酶（Col Ⅰ） mRNA表达及ALP活性和细胞基质钙含量行重复测量方法分析发现，时间点间、组间、组间×时间点间差异均有统计学意义（P < 0.05）；与BMMSCs+PBS相比，BMMSCs+EXO （25、50 μg/mL）组在第1、3、7天的CXCL12、GM-CSF、RUNX2、ALP和Col ⅠmRNA水平下调，IL-6 mRNA水平上调，差异有统计学意义（P < 0.05）。与BMMSCs+EXO （25 μg/mL）组相比，BMMSCs+EXO （50 μg/mL）组CXCL12 （3 d：0.42±0.11比0.26±0.12，7 d：0.39±0.11比0.24±0.10）、RUNX2 （3 d：0.24±0.10比0.10±0.03）和Col ⅠmRNA水平（1 d：0.74±0.19比0.58±0.20，7 d：0.12±0.16比0.08±0.16）下调，IL-6 mRNA水平（1 d：1.36±0.54比2.14±0.42，3 d：2.46±0.47比3.30±0.42，7 d：3.62±0.49比4.30±0.48）上调，差异有统计学意义（P < 0.05）。Western blot发现，与BMMSCs+PBS相比，BMMSCs+EXO （25、50 μg/mL）组CXCL12 （1.00比0.54±0.10、0.32±0.08）、GM-CSF （1.00比0.46±0.12、0.42±0.03）、RUNX2 （1.00比0.57±0.12、0.45±0.23）、ALP （1.00比0.46±0.06、0.35±0.23）和ColⅠ表达（1.00比0.74±0.15、0.53±0.23）降低，IL-6表达（1.00比5.24±0.25、10.27±0.13）增加，差异有统计学意义（P < 0.05）。与BMMSCs+EXO （25 μg/mL）组相比，BMMSCs+EXO （50 μg/mL）组CXCL12表达（0.54±0.10比0.32±0.08）降低，IL-6表达（5.24±0.25比10.27±0.13）增加，差异有统计学意义（P均< 0.05）。此外，与BMMSCs+PBS组相比，BMMSCs+EXO （25、50 μg/mL）组ALP活性（7 d：1.75±0.58比0.72±0.18、0.58±0.16，14 d：2.78±0.75比1.50±0.32、0.83±0.30）和细胞基质钙含量（14 d：2.73±0.68比1.43±0.42、0.85±0.40）降低，差异有统计学意义（P < 0.05）。

结论

K562细胞来源的EXO影响BMMSCs支持造血和成骨相关因子的表达，抑制了BMMSCs的成骨分化，并且有可能影响其支持造血功能。

关键词: 慢性粒细胞白血病, 骨髓间充质干细胞, 外泌体, 造血, 成骨

Objective

This study was aimed to investigate the effects of K562 cell-derived exosomes on the expression of genes supporting hemopoiesis and osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs) .

Methods

The exosomes in the supernatant of K562 cell culture were isolated by ultracentrifugation and identified. Osteogenic differentiation of BMMSCs was induced in vitro. According to whether exosomes were added, three groups were formed: BMMSCs+PBS, BMMSCs+EXO (25 μg/mL) , and BMMSCs+EXO (50 μg/mL) . The expression of hemopoiesis and osteogenesis-supporting genes in BMMSCs was detected by RT-PCR and Western Blot. ALP activity and cell matrix calcium content were determined by ELISA. Repeated measures ANOVA was used to examine mean differences at different time points, ANOVA analysis to detect differences among multiple groups, and Tukey's test was used for pairwise comparison between groups.

Results

The CXCL12, GM-CSF, IL-6, RUNX2, ALP and ColⅠmRNA expression, alkaline phosphatase activity and cell matrix calcium content in the three groups at each time point were analyzed by repeated measurements and it was found that the differences between time points, groups, and groups×time points were statistically significant (P < 0.05) . Compared with BMMSCs+PBS, on day 1, 3 and 7, CXCL12, GM-CSF, RUNX2, ALP and ColⅠmRNA levels were down-regulated and IL-6 mRNA levels were up-regulated in the BMMSCs+EXO (25 μg/mL and 50 μg/mL) group, and the difference was statistically significant (P < 0.05) . Compared with the BMMSCs+EXO (25 μg/mL) group, the CXCL12 (3 d: 0.42±0.11 vs 0.26±0.12; 7 d: 0.39±0.11 vs 0.24±0.10) , RUNX2 (3 d: 0.24±0.10 vs 0.10±0.03) and ColⅠ (1 d: 0.74±0.19 vs 0.58±0.20; 7 d: 0.12±0.16 vs 0.08±0.16) mRNA levels were down-regulated and IL-6 (1 d:1.36±0.54 vs 2.14±0.42; 3 d:2.46±0.47 vs 3.30±0.42; 7 d:3.62±0.49 vs 4.30±0.48) mRNA levels were up-regulated in the BMMSCs+EXO (50 μg/mL) group, and the difference was statistically significant (P < 0.05) . Compared with BMMSCs+PBS, the expressions of CXCL12 (1.00 vs 0.54±0.10, 0.32±0.08) , GM-CSF (1.00 vs 0.46±0.12, 0.42±0.03) , RUNX2 (1.00 vs 0.57±0.12, 0.45±0.23) , ALP (1.00 vs 0.46±0.06, 0.35±0.23) and ColⅠ (1.00 vs 0.74±0.15,0.53±0.23) were decreased and IL-6 (1.00 vs 5.24±0.25, 10.27±0.13) was increased in the BMMSCs+EXO (25 μg/mL and 50 μg/mL) group, and the difference was statistically significant (P < 0.05) . Compared with the BMMSCs+EXO (25 μg/ml) group, the expression of CXCL12 (0.54±0.10 vs 0.32±0.08) was decreased and IL-6 (5.24±0.25 vs 10.27±0.13) was increased in the BMMSCs+EXO (50 μg/mL) group, and the difference was statistically significant (P < 0.05) . In addition, compared with BMMSCs+PBS, ALP activity (7 d: 1.75±0.58 vs 0.72±0.18, 0.58±0.16; 14 d: 2.78±0.75 vs 1.50±0.32, 0.83±0.30) and cell matrix calcium content (14 d: 2.73±0.68 vs 1.43±0.42, 0.85±0.40) in the BMMSCs+EXO (25 μg/mL and 50 μg/mL) group were decreased, and the difference was statistically significant (P < 0.05) .

Conclusion

K562 cell-derived exosomes affect the expression of hemopoiesis and osteogenesis-supporting genes in BMMSCs, thereby inhibiting osteogenic differentiation of BMMSCs, and may affect the function supporting hemopoiesis.

Key words: Chronic myeloid leukemia, Bone marrow mesenchymal stem cells, Exosome, Hemopoiesis, Osteogenesis

表1 引物序列

基因	序列（5'→3'）	预期扩增产物长度（bp）
CXCL12	上游ACAGATGCCCATGCCGATTCT	159
	下游CCTGAATCCACTTTAGCTTCGGGT
GM-CSF	上游TCTCAGAAATGTTTGACCTAAC	142
	下游GCCCTTGAGCTTGGTGAG
IL-6	上游GGAGACTTGCCTGGTGAAAA	179
	下游CAGGGGTGGTTATTGCATCT
RUNX2	上游TGTCATGGCGGGTAACGAT	147
	下游AAGACGGTTATGGTCAAGGTGAA
ALP	上游ACGTGGCTAAGAATGTCATC	476
	下游CTGGTAGGCGATGTCCTTA
Col Ⅰ	上游GAGGGCCAAGACGAAGACATC	140
	下游CAGATCACGTCATCGCACAAC
GAPDH	上游ATTTGGTCGTATTGGGCG	124
	下游TGGAAGATGGTGATGGGATT

表1 引物序列

基因	序列（5'→3'）	预期扩增产物长度（bp）
CXCL12	上游ACAGATGCCCATGCCGATTCT	159
	下游CCTGAATCCACTTTAGCTTCGGGT
GM-CSF	上游TCTCAGAAATGTTTGACCTAAC	142
	下游GCCCTTGAGCTTGGTGAG
IL-6	上游GGAGACTTGCCTGGTGAAAA	179
	下游CAGGGGTGGTTATTGCATCT
RUNX2	上游TGTCATGGCGGGTAACGAT	147
	下游AAGACGGTTATGGTCAAGGTGAA
ALP	上游ACGTGGCTAAGAATGTCATC	476
	下游CTGGTAGGCGATGTCCTTA
Col Ⅰ	上游GAGGGCCAAGACGAAGACATC	140
	下游CAGATCACGTCATCGCACAAC
GAPDH	上游ATTTGGTCGTATTGGGCG	124
	下游TGGAAGATGGTGATGGGATT

图1 外泌体的特征

图2 K562细胞来源的外泌体对BMMSCs支持造血和成骨分化相关因子蛋白表达的影响

表2 K562细胞来源的外泌体对BMMSCs CXCL12、GM-CSF、IL-6 mRNA表达的影响（ ± s）

分组	实验次数	CXCL12			GM-CSF			IL-6
分组	实验次数	1 d	3 d	7 d	1 d	3 d	7 d	1 d	3 d	7 d
BMMSCs+PBS	3	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
BMMSCs+EXO （25 g/mL）	3	0.83±0.02	0.43±0.04^a	0.41±0.07^a	0.84±0.05^a	0.32±0.06^a	0.25±0.03^a	1.43±0.10^a	2.45±0.45^a	3.62±0.19^a
BMMSCs+EXO （50 g/mL）	3	0.79±0.03^a	0.24±0.05^ab	0.25±0.03^ab	0.74±0.03^ab	0.23±0.04^a	0.18±0.03^ab	2.19±0.20^ab	3.37±0.45^ab	4.34±0.29^ab
时间点间（F/P）		367.423/< 0.001			461.006/< 0.001			234.057/< 0.001
组间×时间点间（F/P）		92.341/< 0.001			115.545/< 0.001			58.901/< 0.001
组间（F/P）		429.316/< 0.001			914.395/< 0.001			81.569/< 0.001

表2 K562细胞来源的外泌体对BMMSCs CXCL12、GM-CSF、IL-6 mRNA表达的影响（ ± s）

分组	实验次数	CXCL12			GM-CSF			IL-6
分组	实验次数	1 d	3 d	7 d	1 d	3 d	7 d	1 d	3 d	7 d
BMMSCs+PBS	3	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
BMMSCs+EXO （25 g/mL）	3	0.83±0.02	0.43±0.04^a	0.41±0.07^a	0.84±0.05^a	0.32±0.06^a	0.25±0.03^a	1.43±0.10^a	2.45±0.45^a	3.62±0.19^a
BMMSCs+EXO （50 g/mL）	3	0.79±0.03^a	0.24±0.05^ab	0.25±0.03^ab	0.74±0.03^ab	0.23±0.04^a	0.18±0.03^ab	2.19±0.20^ab	3.37±0.45^ab	4.34±0.29^ab
时间点间（F/P）		367.423/< 0.001			461.006/< 0.001			234.057/< 0.001
组间×时间点间（F/P）		92.341/< 0.001			115.545/< 0.001			58.901/< 0.001
组间（F/P）		429.316/< 0.001			914.395/< 0.001			81.569/< 0.001

表3 K562细胞来源的外泌体对BMMSCs CXCL12、GM-CSF和IL-6蛋白表达的影响（ ± s）

分组		实验次数	CXCL12	GM-CSF	IL-6
BMMSCs+PBS		3	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）		3	0.53±0.06^a	0.46±0.12^a	5.25±0.26^a
BMMSCs+EXO （50 μg/mL）		3	0.35±0.05^ab	0.42±0.04^a	10.27±0.13^ab
	F值		166.180	59.025	2293.417
	P值		< 0.001	< 0.001	< 0.001

表3 K562细胞来源的外泌体对BMMSCs CXCL12、GM-CSF和IL-6蛋白表达的影响（ ± s）

分组		实验次数	CXCL12	GM-CSF	IL-6
BMMSCs+PBS		3	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）		3	0.53±0.06^a	0.46±0.12^a	5.25±0.26^a
BMMSCs+EXO （50 μg/mL）		3	0.35±0.05^ab	0.42±0.04^a	10.27±0.13^ab
	F值		166.180	59.025	2293.417
	P值		< 0.001	< 0.001	< 0.001

表4 K562细胞来源的外泌体对BMMSCs RUNX2、ALP和Col Ⅰ mRNA表达的影响（ ± s）

分组		实验次数	RUNX2			ALP			Col Ι
分组		实验次数	1 d	3 d	7 d	1 d	3 d	7 d	1 d	3 d	7 d
BMMSCs+PBS		3	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）		3	0.54±0.05^a	0.24±0.09^a	0.14±0.09^a	0.74±0.10^a	0.27±0.09^a	0.22±0.02^a	0.77±0.10^a	0.26±0.08^a	0.13±0.02^a
BMMSCs+EXO （50 μg/mL）		3	0.44±0.03^ab	0.10±0.03^ab	0.11±0.07^a	0.64±0.02^a	0.18±0.09^a	0.13±0.07^a	0.56±0.06^ab	0.16±0.07^ab	0.11±0.01^a
	时间点间（F/P）		72.865/< 0.001			83.280/< 0.001			87.076/< 0.001
	组间×时间点间（F/P）		19.161/< 0.001			20.834/< 0.001			23.016/< 0.001
	组间（F/P）		456.905/< 0.001			576.768/< 0.001			11045.320/< 0.001

表4 K562细胞来源的外泌体对BMMSCs RUNX2、ALP和Col Ⅰ mRNA表达的影响（ ± s）

分组		实验次数	RUNX2			ALP			Col Ι
分组		实验次数	1 d	3 d	7 d	1 d	3 d	7 d	1 d	3 d	7 d
BMMSCs+PBS		3	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）		3	0.54±0.05^a	0.24±0.09^a	0.14±0.09^a	0.74±0.10^a	0.27±0.09^a	0.22±0.02^a	0.77±0.10^a	0.26±0.08^a	0.13±0.02^a
BMMSCs+EXO （50 μg/mL）		3	0.44±0.03^ab	0.10±0.03^ab	0.11±0.07^a	0.64±0.02^a	0.18±0.09^a	0.13±0.07^a	0.56±0.06^ab	0.16±0.07^ab	0.11±0.01^a
	时间点间（F/P）		72.865/< 0.001			83.280/< 0.001			87.076/< 0.001
	组间×时间点间（F/P）		19.161/< 0.001			20.834/< 0.001			23.016/< 0.001
	组间（F/P）		456.905/< 0.001			576.768/< 0.001			11045.320/< 0.001

表5 K562细胞来源的外泌体对BMMSCs RUNX2、ALP和Col Ⅰ蛋白表达的影响（ ± s）

分组	实验次数	RUNX2	ALP	Col Ι
BMMSCs+PBS	3	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）	3	0.57±0.10^a	0.47±0.06^a	0.74±0.05^a
BMMSCs+EXO （50 μg/mL）	3	0.45±0.07^a	0.35±0.03^ab	0.54±0.03^ab
F值		50.517	239.267	140.824
P值		< 0.001	< 0.001	< 0.001

表5 K562细胞来源的外泌体对BMMSCs RUNX2、ALP和Col Ⅰ蛋白表达的影响（ ± s）

分组	实验次数	RUNX2	ALP	Col Ι
BMMSCs+PBS	3	1.00	1.00	1.00
BMMSCs+EXO （25 μg/mL）	3	0.57±0.10^a	0.47±0.06^a	0.74±0.05^a
BMMSCs+EXO （50 μg/mL）	3	0.45±0.07^a	0.35±0.03^ab	0.54±0.03^ab
F值		50.517	239.267	140.824
P值		< 0.001	< 0.001	< 0.001

表6 K562细胞来源的外泌体对BMMSCs的ALP活性和细胞基质钙含量的影响

分组		实验次数	ALP活性（mU/mL）			细胞基质钙含量（μmol/dL）
分组		实验次数	1 d	7 d	14 d	1 d	7 d	14 d
BMMSCs+PBS		3	0.28±0.05	1.74±0.39	2.78±0.25	0.25±0.10	1.02±0.20	2.74±0.45
BMMSCs+EXO （25 μg/mL）		3	0.19±0.07	0.74±0.07^a	1.51±0.11^a	0.19±0.05	0.73±0.06^a	1.43±0.12^a
BMMSCs+EXO （50 μg/mL）		3	0.16±0.02	0.59±0.05^a	0.84±0.07^ab	0.16±0.03	0.58±0.06^a	0.78±0.06^ab
	时间点间（F/P）		140.513/< 0.001			103.597/< 0.001
	组间×时间点间（F/P）		18.402/< 0.001			22.332/< 0.001
	组间（F/P）		277.806/< 0.001			175.910/< 0.001

表6 K562细胞来源的外泌体对BMMSCs的ALP活性和细胞基质钙含量的影响

分组		实验次数	ALP活性（mU/mL）			细胞基质钙含量（μmol/dL）
分组		实验次数	1 d	7 d	14 d	1 d	7 d	14 d
BMMSCs+PBS		3	0.28±0.05	1.74±0.39	2.78±0.25	0.25±0.10	1.02±0.20	2.74±0.45
BMMSCs+EXO （25 μg/mL）		3	0.19±0.07	0.74±0.07^a	1.51±0.11^a	0.19±0.05	0.73±0.06^a	1.43±0.12^a
BMMSCs+EXO （50 μg/mL）		3	0.16±0.02	0.59±0.05^a	0.84±0.07^ab	0.16±0.03	0.58±0.06^a	0.78±0.06^ab
	时间点间（F/P）		140.513/< 0.001			103.597/< 0.001
	组间×时间点间（F/P）		18.402/< 0.001			22.332/< 0.001
	组间（F/P）		277.806/< 0.001			175.910/< 0.001

1	Agarwal A, Fleischman AG, Petersen CL, et al. Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML[J]. Blood, 2012, 120(13):2658-2668.
2	Corrado C, Saieva L, Raimondo S, et al. Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor[J]. J Cell Mol Med, 2016, 20(10):1829-1839.
3	Seke Etet PF, Vecchio L, Nwabo Kamdje AH. Signaling pathways in chronic myeloid leukemia and leukemic stem cell maintenance: Key role of stromal microenvironment[J]. Cell Signal, 2012, 24(9):1883-1888.
4	Qazi KR, Torregrosa Paredes P, Dahlberg B, et al. Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis[J]. Thorax, 2010, 65(11):1016-1024.
5	Turpin D, Truchetet M, Faustin B, et al. Role of extracellular vesicles in autoimmune diseases[J]. Autoimmun Rev, 2016, 15(2):174-183.
6	Zheng X, Chen F, Zhang Q, et al. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease[J]. Protein Cell, 2017, 8(9):686-695.
7	Shrivastava S, Morris KV. The Multifunctionality of exosomes; from the garbage bin of the cell to a next generation gene and cellular therapy[J]. Genes, 2021, 12(2):173. doi: 10.3390/genes12020173.
8	Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function[J]. Nat Rev Immunol, 2002, 2(8):569-579.
9	Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go[J]. Cell, 2016, 164(6):1226-1232.
10	Jiang Y, Liu J, Lin J, et al. K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711[J]. Biochem Biophys Res Commun, 2020, 521(3):584-589.
11	Tu C, Du Z, Zhang H, et al. Endocytic pathway inhibition attenuates extracellular vesicle-induced reduction of chemosensitivity to bortezomib in multiple myeloma cells[J]. Theranostics, 2021, 11(5):2364-2380.
12	Rashid MH, Borin TF, Ara R, et al. Critical immunosuppressive effect of MDSCderived exosomes in the tumor microenvironment[J]. Oncol Rep, 2021, 45(3):1171-1181.
13	Yu L, Sui B, Fan W, et al. Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p[J]. J Extracell Vesicles, 2021, 10(3):e12056. doi: 10.1002/jev2.12056.
14	Kumar B, Garcia M, Weng L, et al. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion[J]. Leukemia, 2017, 32(3):575-587.
15	Lozzio BB, Lozzio CB. Properties of the K562 cell line derived from a patient with chronic myeloid leukemia[J] Int J Cancer, 1977, 19(1):136. doi: 10.1002/ijc.2910190119.
16	Mineo M, Garfield SH, Taverna S, et al. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion[J]. Angiogenesis, 2012, 15(1):33-45.
17	Thery C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids[J]. Curr Protoc Cell Biol, 2006, Chapter 3:Unit 3.22. doi: 10.1002/0471143030.
18	Whiteside TL. Tumor-derived exosomes and their role in cancer progression[J] Adv Clin Chem, 2016, 74:103-41.
19	Arnulf B, Lecourt S, Soulier J, et al. Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma[J]. Leukemia, 2007, 21(1):158-163.
20	Wang J, De Veirman K, Faict S, et al. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression[J]. J Pathol, 2016, 239(2):162-173.
21	Boyiadzis M, Whiteside TL. Exosomes in acute myeloid leukemia inhibit hematopoiesis[J]. Curr Opin Hematol, 2018, 25(4):279-284.
22	Cho B, Kim H, Konopleva M. Targeting the CXCL12/CXCR4 axis in acute myeloid leukemia: from bench to bedside[J]. Korean J Intern Med, 2017, 32(2):248-257.
23	Huan J, Hornick NI, Goloviznina NA, et al. Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes[J]. Leukemia, 2015, 29(12):2285-2295.
24	Taverna S, Amodeo V, Saieva L, et al. Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells[J]. Mol Cancer, 2014, 13:169. doi: 10.1186/1476-4598-13-169.
25	Jafarzadeh N, Safari Z, Pornour M, et al. Alteration of cellular and immune-related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes[J]. J Cell Physiol, 2019, 234(4):3697-3710.
26	Cho SW, Pirih FQ, Koh AJ, et al. The soluble interleukin-6 receptor is a mediator of hematopoietic and skeletal actions of parathyroid hormone[J]. J Biol Chem, 2013, 288(10):6814-6825.
27	O'Hagan-Wong K, Nadeau S, Carrier-Leclerc A, et al. Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells' homeostasis[J]. Oncotarget, 2016, 7(12):13285-13296.
28	Zhu F, McCaw L, Spaner DE, et al. Targeting the IL-17/IL-6 axis can alter growth of Chronic Lymphocytic Leukemia in vivo/in vitro[J]. Leuk Res, 2018, 66:28-38.
29	Wang HQ, Jia L, Li YT, et al. Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia[J]. J Cell Physiol, 2019, 234(8):13994-14006.
30	Kassem NM, Ayad AM, El Husseiny NM, et al. Role of granulocyte-macrophage colony-stimulating factor in acute myeloid leukemia/myelodysplastic syndromes[J] J Glob Oncol, 2018, 4:1-6.
31	Xia P, Gu R, Zhang W, et al. MicroRNA-200c promotes osteogenic differentiation of human bone mesenchymal stem cells through activating the AKT/beta-Catenin signaling pathway via downregulating Myd88[J]. J Cell Physiol, 2019, 234(12):22675-22686.
32	Almalki SG, Agrawal DK. Key transcription factors in the differentiation of mesenchymal stem cells[J]. Differentiation, 2016, 92(1-2):41-51.
33	Murakami J, Ishii M, Suehiro F, et al. Vascular endothelial growth factor-C induces osteogenic differentiation of human mesenchymal stem cells through the ERK and RUNX2 pathway[J]. Biochem Biophys Res Commun, 2017, 484(3):710-718.
34	Krause U, Seckinger A, Gregory CA. Assays of osteogenic differentiation by cultured human mesenchymal stem cells[J]. Methods Mol Biol, 2011, 698:215-230.

[1]	王岩, 马剑雄, 郎爽, 董本超, 田爱现, 李岩, 孙磊, 靳洪震, 卢斌, 王颖, 柏豪豪, 马信龙. 外泌体在骨质疏松症诊疗中应用的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 673-678.
[2]	贺敬龙, 孙炜, 高明宏, 谢伟, 姜骆永, 何琦非, 岳家吉. 外泌体非编码RNA在骨关节炎发病机制中的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(04): 520-527.
[3]	代雯荣, 赵丽娟, 李智慧. 细胞外囊泡对胚胎着床影响的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 616-620.
[4]	汪国建, 谭雨龙, 龙爽, 吕晓凡, 赵娜, 冉新泽, 王军平, 王涛. 高温高湿环境暴露对重度放创复合伤小鼠损伤恢复的影响[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 285-292.
[5]	全勇, 冉新泽, 胡梦佳, 陈芳, 陈乃成, 廖伟年, 陈默, 申明强, 陈石磊, 王崧, 王军平. 低氧习服在小鼠造血干细胞急性放射损伤修复中的作用观察[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 293-298.
[6]	高雷, 李芳, 巴雅力嘎, 李全, 巴特. 干细胞源性外泌体在创伤修复中免疫作用的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 364-367.
[7]	黄瑞娟, 德奇, 巴特, 周彪. 对人脐带间充质干细胞外泌体影响热损伤人皮肤成纤维细胞迁移的分析[J]. 中华损伤与修复杂志(电子版), 2023, 18(03): 229-234.
[8]	纪文鑫, 王茂, 邱春丽, 李尚鹏, 代引海. 血清外泌体circ PVT1与circ 0014606在三阴性乳腺癌中的表达及临床意义[J]. 中华普外科手术学杂志(电子版), 2023, 17(03): 267-271.
[9]	孔欣, 宋宝全, 刘吟, 张剑, 仇惠英, 吴德沛. 异基因造血干细胞移植并发难治性呃逆一例[J]. 中华移植杂志(电子版), 2023, 17(04): 253-255.
[10]	黄承路, 廖飞, 刘显平, 王志强. 血清外泌体Has_circ_0060937过度表达与NSCLC转移和不良预后的关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 490-494.
[11]	刘文慧, 吴涛, 张曦. 间充质干细胞联合血小板生成素受体激动剂在异基因造血干细胞移植后血小板恢复中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 242-246.
[12]	崔燕妮, 任颜, 梁凤婷, 覃艳红, 王宏伟. 脐带血源性产品Omidubicel的临床研发进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 178-182.
[13]	王楚风, 蒋安. 原发性肝癌的分子诊断[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 499-503.
[14]	陈客宏. 干细胞外泌体防治腹膜透析腹膜纤维化新技术研究[J]. 中华肾病研究电子杂志, 2023, 12(03): 180-180.
[15]	高雷, 李全, 巴雅力嘎, 陈强, 侯智慧, 曹胜军, 巴特. 重度烧伤患者血小板外泌体对凝血功能调节作用的初步研究[J]. 中华卫生应急电子杂志, 2023, 09(03): 149-154.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

The effects of K562 cell-derived exosomes on the hematopoietic and osteogenic gene expressions of bone marrow mesenchymal stem cells

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

The effects of K562 cell-derived exosomes on the hematopoietic and osteogenic gene expressions of bone marrow mesenchymal stem cells