Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

Abstract

The aim of the present study was to investigate the therapeutic effect of chlorogenic acid on hormonal femoral head necrosis and its protection of osteoblasts. The study established a femoral head necrosis model in Wistar rats using endotoxin and prednisolone acetate. The rats were divided into five groups and were treated with different concentrations of chlorogenic acid (1, 10 and 20 mg/kg). The main detected indicators were the blood rheology, bone mineral density, and the hydroxyproline and hexosamine (HOM) contents. At a cellular level, osteoblasts were cultured and treated by drug-containing serum. Subsequently, cell proliferation and the osteoblast cycle were measured using flow cytometry, and the protein expression levels of Bax and B-cell lymphoma 2 (Bcl-2) were detected using western blotting. Chlorogenic acid at a concentration of 20 mg/kg (high-dose) enhanced the bone mineral density of the femoral head and femoral neck following ischemia. Simultaneously, blood flow following the injection of prednisolone acetate was significantly improved, and the HOM contents of the high-dose chlorogenic acid group were significantly different. The results from the flow cytometry analysis indicated that chlorogenic acid can efficiently ameliorate hormone-induced necrosis. The osteoblasts were isolated and cultured. The MTT colorimetric assay showed that chlorogenic acid at different densities can increase the proliferation capabilities of osteoblasts and accelerate the transition process of G/G phase to S phase, as well as enhance mitosis and the regeneration of osteoblasts. Western blotting detection indicated that chlorogenic acid may prohibit the decrease of Bcl-2 and the increase of Bax during apoptosis, thereby inhibiting osteoblast apoptosis and preventing the deterioration of femoral head necrosis. In conclusion, chlorogenic acid at the density of 20 mg/kg is effective in the treatment of hormonal femoral head necrosis, which may be applicable for future treatment.

Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

“…Potential metabolites were identi ed based on accurate mass measurements via UHPLC-MS/MS, comparison with theoretical isotopic patterns, MS/MS fragment or comparison with HMDB database, metlin database, lipid maps and chemspider database. Through identi cation, 11 potential biomarkers were screened out, mainly contained phosphatidylcholine (PC), which were the closely related to the SANFH [4,27].…”

“…The lipocytes were representative change in the experiment process. The steroids induced a signi cant enlargement of the adipocyte size and a fat accumulation in the bone marrow, which contributes to an intraosseous hypertension and a decreased blood ow [2][3][4]. The results of our study support the previous research ndings that the use of lovastatin with SANFH could have a potential to preserve the bone mass by adjusting the lipid metabolism, inhibiting adipogenesis and delaying the osteocyte apoptosis to decrease the incidence of osteonecrosis and it is meaningful for patients need long-term or high-dose glucocorticoid therapy.…”

“…Glucocorticoid -induced necrosis of the femoral head is di cult miscellaneous diseases in clinical diagnose [1]. The glucocorticoid is one of the steroid and plays an important role on clinical treatment of organ grafting, systemic lupus erythematosus, rheumatic arthritis, dermatomyositis, myasthenia, but long time or excess use of the glucocorticoid could result in escalation of osteonecrosis [2][3][4][5]. Researchers have paid more attention to steroid-associated osteonecrosis in the recently years.…”

Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

“…The steroids induced a significant enlargement of the adipocyte size and a fat accumulation in the bone marrow, which contributes to an intraosseous hypertension and a decreased blood flow [2][3][4].…”

“…Glucocorticoid -induced necrosis of the femoral head is difficult miscellaneous diseases in clinical diagnose [1]. The glucocorticoid is one of the steroid and plays an important role on clinical treatment of organ grafting, systemic lupus erythematosus, rheumatic arthritis, dermatomyositis, myasthenia, but long time or excess use of the glucocorticoid could result in escalation of osteonecrosis [2][3][4][5].…”