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多糖能够抑制大鼠间充质干细胞来源的外泌体诱导的破骨细胞分化。

polysaccharide enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells.

机构信息

Department of Orthopedic Surgery, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, PR China.

出版信息

Pharm Biol. 2022 Dec;60(1):1303-1316. doi: 10.1080/13880209.2022.2093385.

DOI:10.1080/13880209.2022.2093385
PMID:35801991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9272931/
Abstract

CONTEXT

F.C. How. (MO) (Rubiaceae) can strengthen bone function.

OBJECTIVE

To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP).

MATERIALS AND METHODS

Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [ = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for studies.

RESULTS

MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%,  < 0.01), elevated the bone volume to tissue volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean connectivity density (Conn.D) (40-86%,  < 0.01), decreased the mean trabecular separation/spacing (Tb.Sp) (22-37%,  < 0.01), increased the cortical bone continuity (35-90%,  < 0.01) and elevated RUNX family transcription factor 2 and RANK levels (5-12%,  < 0.01), but suppressed matrix metallopeptidase 9 and cathepsin K levels (9-20%,  < 0.01) in femur tissues. BMSC-Exo from MOP-treated rats (MOP-Exo) suppressed osteoclastic differentiation and proliferation of BMMs. The downregulation of microRNA-101-3p (miR-101-3p) or the upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) blocked the functions of MOP-Exo.

DISCUSSION AND CONCLUSIONS

MOP inhibits osteoclastic differentiation and could potentially be used for osteoporosis management. This suppression may be enhanced by the upregulation of miR-101-3p or the inhibition of PTGS2.

摘要

背景

五指牛奶(MO)(茜草科)可增强骨骼功能。

目的

研究 MO 多糖(MOPs)在糖皮质激素诱导骨质疏松症(GIOP)大鼠中的作用机制和效果。

材料和方法

采用腹腔注射 5、15 或 45ml/kg MOP[剂量分别为 15 只,每 2 天 1 次,共 8 周]的方法建立 GIOP 大鼠模型。检测大鼠体重和骨组织形态学变化。收集骨髓间充质干细胞(BMSC)来源的外泌体(Exo)并进行鉴定。诱导骨髓来源的巨噬细胞(BMM)分化为破骨细胞,用 BMSC-Exo 处理进行研究。

结果

MOP 降低了体重(5、15 或 45mg/kg MOP 与磷酸盐缓冲液相比:8%、15%和 25%,<0.01),增加了骨体积/组织体积(BV/TV)、平均骨小梁厚度(Tb.Th)、平均骨小梁数量(Tb.N)和平均连接密度(Conn.D)(40-86%,<0.01),降低了平均骨小梁间距(Tb.Sp)(22-37%,<0.01),增加了皮质骨连续性(35-90%,<0.01),并提高了 RUNX 家族转录因子 2 和 RANK 水平(5-12%,<0.01),但降低了股骨组织中基质金属蛋白酶 9 和组织蛋白酶 K 水平(9-20%,<0.01)。来自 MOP 处理大鼠的 BMSC-Exo(MOP-Exo)抑制了破骨细胞的分化和 BMM 的增殖。下调 microRNA-101-3p(miR-101-3p)或上调前列腺素内过氧化物合酶 2(PTGS2)可阻断 MOP-Exo 的功能。

讨论和结论

MOP 抑制破骨细胞分化,可能用于骨质疏松症的治疗。这种抑制作用可能通过 miR-101-3p 的上调或 PTGS2 的抑制来增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/7fd6e8cfe357/IPHB_A_2093385_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/2d51a5ab713a/IPHB_A_2093385_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/569deb0b5ec6/IPHB_A_2093385_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/8a4bf8d64502/IPHB_A_2093385_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/00972dbd5d72/IPHB_A_2093385_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/0ab988391c3f/IPHB_A_2093385_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/a9280329c438/IPHB_A_2093385_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/c0a74e34180b/IPHB_A_2093385_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/f250d139a41f/IPHB_A_2093385_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/7fd6e8cfe357/IPHB_A_2093385_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/2d51a5ab713a/IPHB_A_2093385_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/569deb0b5ec6/IPHB_A_2093385_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/8a4bf8d64502/IPHB_A_2093385_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/00972dbd5d72/IPHB_A_2093385_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/0ab988391c3f/IPHB_A_2093385_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/a9280329c438/IPHB_A_2093385_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/c0a74e34180b/IPHB_A_2093385_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/f250d139a41f/IPHB_A_2093385_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c07d/9272931/7fd6e8cfe357/IPHB_A_2093385_F0009_C.jpg

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