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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:61

Enthalten in:

Pharmaceutical biology - 61(2023), 1 vom: 31. Dez., Seite 568-580

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Bone marrow mesenchymal stem cell
Journal Article
MAKP signalling
MiR122-5p
MicroRNAs
Osteoblastic and adipogenic differentiation
SPRY2

Anmerkungen:

Date Completed 03.04.2023

Date Revised 11.04.2023

published: Print

Citation Status MEDLINE

doi:

10.1080/13880209.2023.2190773

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM355042584