Regulation of JAK2/STAT3 signaling pathway by polydatin in the treatment of hormone-induced femoral head necrosis in rats.
10.12200/j.issn.1003-0034.20240924
- Author:
Xiang-Jun YANG
1
;
Cong-Yue WANG
2
;
Xi-Lin XU
3
;
Hai HU
1
;
Yi-Wei SHEN
4
;
Xiao-Feng ZHANG
5
,
6
,
7
,
8
Author Information
1. The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang, China.
2. Harbin Hospital of Traditional Chinese Medicine, Harbin 150070, Heilongjiang, China.
3. The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150030, Heilongjiang, China.
4. The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang, China; The Fourth Affiliated Hospital of Tianjin University of Chinese Medicine, Tianjin 300451, China.
5. The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang, China;
6. Harbin Hospital of Traditional Chinese Medicine, Harbin 150070, Heilongjiang, China;
7. The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150030, Heilongjiang, China;
8. The Fourth Affiliated Hospital of Tianjin University of Chinese Medicine, Tianjin 300451, China.
- Publication Type:Journal Article
- Keywords:
Bone tissue protection;
JAK2/STAT3 signaling pathway;
Osteogenic differentiation;
Polygonum cuspidatum glycoside;
Steroid-induced osteonecrosis of the femoral head
- MeSH:
Animals;
Male;
Janus Kinase 2/physiology*;
Rats, Sprague-Dawley;
Rats;
Signal Transduction/drug effects*;
Glucosides/pharmacology*;
STAT3 Transcription Factor/genetics*;
Femur Head Necrosis/chemically induced*;
Stilbenes/pharmacology*
- From:
China Journal of Orthopaedics and Traumatology
2025;38(2):195-203
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the therapeutic effect of polygonum cuspidatum glycoside on steroid-induced osteonecrosis of the femoral head(SONFH) in rats and its potential mechanism of protecting bone tissue by regulating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway(JAK2/STAT3).
METHODS:Fifty male SD rats were randomly divided into control group, model group, low-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-L), high-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-H), and polygonum cuspidatum glycoside-H+Colivelin (JAK2/STAT3 pathway activator) group. SONFH model was induced by lipopolysaccharide and dexamethasone. The treatment groups were given polygonum cuspidatum glycoside orally(polygonum cuspidatum glycoside-L 10 mg·kg-1, polygonum cuspidatum glycoside-H 20 mg·kg-1, and the polygonum cuspidatum glycoside-H+Colivelin group was injected with Colivelin (1 mg·kg-1) intraperitoneally once a day, while the control and model groups were given an equal volume of saline for 6 weeks. The observed indicators included serum calcium(Ca), serum phosphorus (P), alkaline phosphatase, and transforming growth factor β1(TGF-β1) levels, micro-CT scanning, hematoxylin-eosin staining, and Western blot detection of JAK2/STAT3 signaling pathway and osteogenic differentiation marker genes, including Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), and osteopontin (OPN) protein expression.
RESULTS:Compared with the model group, the trabecular bone area percentage in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups was significantly increased, and the empty lacunar rate was significantly decreased (P<0.05). Micro-CT analysis showed that the bone volume fraction, trabecular number, and thickness increased, and the trabecular separation decreased in the polygonum cuspidatum glycoside-treated groups(P<0.05). Serum biochemical tests found that the serum Ca and P concentrations in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups were restored, the alkaline phosphatase levels decreased, and the transforming growth factor β1 levels increased (P<0.05). Western blot analysis showed that polygonum cuspidatum glycoside significantly inhibited the activation of the JAK2/STAT3 signaling pathway in the model group and promoted the expression of osteogenic differentiation marker genes such as Runx2, BMP2, and OPN (P<0.05). Compared with the polygonum cuspidatum glycoside-H group, the improvements in the polygonum cuspidatum glycoside-H+Colivelin group were somewhat weakened, indicating the importance of the JAK2/STAT3 signaling pathway in the action of polygonum cuspidatum glycoside.
CONCLUSION:polygonum cuspidatum glycoside promotes osteogenic differentiation, improves bone microstructure, and has significant therapeutic effects on rat SONFH by regulating the JAK2/STAT3 signaling pathway.
