Bushen Zhuanggu Formula promotes bone repair in nontraumatic osteonecrosis of the femoral head via regulating PKC-RAS-ERK-ETS1-RANKL signaling axis
10.1097/st9.0000000000000076
- Author:
Chu ZHANG
1
;
Zhaochen MA
2
;
Tao LI
2
;
Yudong LIU
2
;
Yan JIA
3
;
Qun LI
2
;
Chunfang LIU
2
;
Ya LIN
4
;
Chunzhu GONG
5
;
Na LIN
2
;
Weiheng CHEN
3
;
Yanqiong ZHANG
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China; College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
3. Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
4. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
5. Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen, China
- Publication Type:Journal Article
- Keywords:
Bushen Zhuanggu Formula;
Nontraumatic osteonecrosis of the femoral head;
Transcriptome;
Based network investigation;
Bone repair;
PKC-RAS-ERK-ETS1-RANKL signaling axis
- From:
Science of Traditional Chinese Medicine
2025;3(3):239-249
- CountryChina
- Language:English
-
Abstract:
Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.
