Abstract
Background Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.
Highlights
Avascular necrosis of the femoral head (ANFH) is one of the most common osteoarthritic diseases worldwide
digital radiography (DR) examination of the femoral head showed early osteonecrosis in the rat steroidinduced avascular necrosis of the femoral head (SANFH) model, and the necrotic area was predominantly located in cancellous bone and the chondral region
Erefore, in this study, a rat model of SANFH was established by intramuscular injection of DEX. e homemade traditional Chinese medicine compound Gujiansan contains a variety of active ingredients that are used for the treatment of bone diseases, and Gujiansan has been successfully used in the clinic to treat thousands of patients with SANFH [7,8,9,10,11,12]
Summary
Avascular necrosis of the femoral head (ANFH) is one of the most common osteoarthritic diseases worldwide. Since the development of hormone drugs and their wide application, the incidence of steroid-induced avascular necrosis of the femoral head (SANFH) has gradually increased, and it frequently occurs in patients receiving high-dose steroid treatment, including patients with systemic lupus erythematosus [3]. The traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroidinduced avascular necrosis of the femoral head (SANFH). Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and timedependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ameliorates SANFH
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