G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis.

Abstract

OBJECTIVES:

Osteonecrosis is also known as avascular necrosis, and two types of cell death are included in the pathogenesis of osteonecrosis: necrosis and apoptosis. Apoptosis in the osteonecrosis of femoral head is thought to be the key determinant of glucocorticoid-induced cortical bone loss. The present study was implemented to evaluate the anti-apoptotic effect of Granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF) in rabbits with steroid-induced osteonecrosis.

METHODS:

In the experiment, osteonecrosis was induced by low-dose lipopolysaccharide and subsequent pulsed high-dose methylprednisolone. Rabbits in preventive medicine group were treated with 100 μg/kg/d G-CSF and 25 μg/kg/d SCF. Then hematological and histomorphometric methods were used to investigate the treatment effects of osteonecrosis. Apoptosis was assessed via quantitative TUNEL staining and activated caspase-3 immunostaining and immunoblotting.

RESULTS:

The results showed that G-CSF/SCF treatment could increase the secretion of serum osteocalcin, but inhibit the expression of serum tartrate-resistant acid phosphatase (TRAP5b). The incidence of osteonecrosis was significantly decreased in Preventive group when compared with Steroid group (42.1% vs. 88.2%). Histomorphometric analysis showed that G-CSF/SCF pre-disposal treatment was able to increase trabecular mineral appositional rate (MAR) and bone formation rate (BFR). Quantitative TUNEL and activated caspase-3 levels showed lower apoptosis in the Preventive group.

CONCLUSIONS:

In conclusion, G-CSF/SCF treatment could inhibit caspase-3-dependent apoptosis in osteocytes to exert beneficial effects in preventing steroid-induced ON in rabbit models.

• Authors: Xinghuo Wu, Shuhua Yang, Hong Wang, Chunqing Meng, Weihua Xu, Deyu Duan, Xianzhe Liu
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 94 Issue 1 Pg. 247-54 (Feb 2013) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 22750282 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Isoenzymes
• Stem Cell Factor
• Osteocalcin
• Granulocyte Colony-Stimulating Factor
• Acid Phosphatase
• Tartrate-Resistant Acid Phosphatase
• Caspase 3
• Methylprednisolone

Topics

• Acid Phosphatase (blood)
• Animals
• Apoptosis (drug effects)
• Caspase 3 (blood)
• Granulocyte Colony-Stimulating Factor (pharmacology, therapeutic use)
• Isoenzymes (blood)
• Methylprednisolone
• Osteocalcin (blood)
• Osteogenesis (drug effects)
• Osteonecrosis (chemically induced, drug therapy, prevention & control)
• Rabbits
• Stem Cell Factor (pharmacology, therapeutic use)
• Tartrate-Resistant Acid Phosphatase