Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes

Lining Wang; Yalan Pan; Mengmig Liu; Jie Sun; Li Yun; Pengcheng Tu; Chengjie Wu; Ziceng Yu; Zhitao Han; Muzhe Li; Yang Guo; Yong Ma

Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes

Lining Wang
, Yalan Pan
, Mengmig Liu
, Jie Sun
, Li Yun
, Pengcheng Tu
, Chengjie Wu
, Ziceng Yu
, Zhitao Han
, Muzhe Li
, Yang Guo
, Yong Ma

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

16 Downloads (Pure)

Abstract

Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. Objective: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. Materials and methods: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 μg exosomes), Exo-WSTLZT (30 μg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. Results: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. Conclusions: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.

Original language	English
Pages (from-to)	568-580
Number of pages	13
Journal	Pharmaceutical Biology
Volume	61
Issue number	1
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Open Access - Access Right Statement

© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Keywords

Bone marrow mesenchymal stem cell
osteoblastic and adipogenic differentiation
MAKP signalling
SPRY2
miR122-5p

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Cite this

@article{b275808b5bfc4478b8ab9acbe6822c05,

title = "Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes",

abstract = "Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. Objective: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. Materials and methods: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 μg exosomes), Exo-WSTLZT (30 μg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. Results: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. Conclusions: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.",

keywords = "Bone marrow mesenchymal stem cell, osteoblastic and adipogenic differentiation, MAKP signalling, SPRY2, miR122-5p",

author = "Lining Wang and Yalan Pan and Mengmig Liu and Jie Sun and Li Yun and Pengcheng Tu and Chengjie Wu and Ziceng Yu and Zhitao Han and Muzhe Li and Yang Guo and Yong Ma",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2023",

language = "English",

volume = "61",

pages = "568--580",

journal = "Pharmaceutical Biology",

issn = "1388-0209",

publisher = "Taylor \& Francis",

number = "1",

}

TY - JOUR

T1 - Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes

AU - Wang, Lining

AU - Pan, Yalan

AU - Liu, Mengmig

AU - Sun, Jie

AU - Yun, Li

AU - Tu, Pengcheng

AU - Wu, Chengjie

AU - Yu, Ziceng

AU - Han, Zhitao

AU - Li, Muzhe

AU - Guo, Yang

AU - Ma, Yong

PY - 2023

Y1 - 2023

N2 - Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. Objective: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. Materials and methods: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 μg exosomes), Exo-WSTLZT (30 μg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. Results: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. Conclusions: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.

AB - Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. Objective: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. Materials and methods: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 μg exosomes), Exo-WSTLZT (30 μg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. Results: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. Conclusions: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.

KW - Bone marrow mesenchymal stem cell

KW - osteoblastic and adipogenic differentiation

KW - MAKP signalling

KW - SPRY2

KW - miR122-5p

UR - https://hdl.handle.net/1959.7/uws:72567

UR - https://www.scopus.com/pages/publications/85151315959

M3 - Article

SN - 1388-0209

VL - 61

SP - 568

EP - 580

JO - Pharmaceutical Biology

JF - Pharmaceutical Biology

IS - 1

ER -

Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes

Abstract

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