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Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis.

He M, Wang J, Wang G, Tian Y, Jiang L, Ren Z, Qiu C, Fu Q - Mol Med Rep (2016)

Bottom Line: The results demonstrated that the GC-treated group had a lower mean weight compared with the control group.In addition, tartarate‑resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group.The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

ABSTRACT
Osteonecrosis, also termed aseptic necrosis, is the cellular death of bone components due to interruption of the blood supply. Glucocorticoid (GC) therapy is a common non-traumatic cause of osteonecrosis. However, the mechanism by which GCs induce osteonecrosis remains to be elucidated. The aim of the present study was to investigate the effects of GCs on osteoclast and osteoblast differentiation and function in a GC‑induced osteonecrosis mouse model. BALB/c male mice (n=40; 4‑weeks‑old) were treated with dexamethasone and asparaginase for 8 weeks. The control group (n=20) was administered normal saline. The results demonstrated that the GC-treated group had a lower mean weight compared with the control group. Morphologically, 16/37 (43%) mice demonstrated significant osteonecrotic lesions in the GC‑treated group. However, osteonecrotic lesions were not observed in the mice of the control group. Furthermore, immunohistochemistry demonstrated that the GC‑treated group had a higher level of osteoprotegerin compared with the control group, without any change in the expression of receptor activator of nuclear factor‑κB ligand. In addition, tartarate‑resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group. Furthermore, the present study demonstrated that GCs increased expression levels of osterix and osteocalcin, and decreased expression of matrix metallopeptidase‑9 to regulate the differentiation and function of osteoblasts and osteoclasts. The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation. Therefore, regulating the differentiation and activity of the osteoclasts may be beneficial to the control and treatment of osteonecrosis.

No MeSH data available.


Related in: MedlinePlus

Effect of GC treatment on the mRNA expression of Runx2, osterix, osteocalcin and MMP-9, as measured by quantitative polymerase chain reaction. The mRNA expression levels of (A) MMP-9 increased, (B) of Runx2 remained the same and the expression levels of (C) osteocalcin and (D) osterix increased in the GC-treated group. The data are presented as the mean ± standard deviation (*P<0.05, vs. the control group). MMP, matrix metallopeptidase; GC, glucocorticoid; Runx2, runt-related transcription factor 2.
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f6-mmr-14-02-1054: Effect of GC treatment on the mRNA expression of Runx2, osterix, osteocalcin and MMP-9, as measured by quantitative polymerase chain reaction. The mRNA expression levels of (A) MMP-9 increased, (B) of Runx2 remained the same and the expression levels of (C) osteocalcin and (D) osterix increased in the GC-treated group. The data are presented as the mean ± standard deviation (*P<0.05, vs. the control group). MMP, matrix metallopeptidase; GC, glucocorticoid; Runx2, runt-related transcription factor 2.

Mentions: In order to identify the in-depth mechanism by which GCs regulate osteoclast differentiation, the mRNA expression levels of Runx2, osterix, osteocalcin and MMP-9 were determined. Runx2 is essential for osteoblastic differentiation and skeletal morphogenesis, and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. Osterix is a zinc finger-containing transcription factor expressed in osteoblasts that serves a role in the osteoblast differentiation pathway. It was suggested that Runx2 acts upstream of osterix, as previous studies demonstrated that in Runx2- mice, osterix is not expressed, whereas in osterix mice, Runx2 is expressed (19). As demonstrated in Fig. 6, the relative mRNA expression of Runx2 in the GC-treated group remained unchanged compared with the control group. In addition, the relative mRNA expression of osterix was increased in the GC-treated group compared with the control group (P<0.05; Fig. 6). The results indicated that GC treatment promoted osteoblast differentiation in the late stage, however had no effect on osteoblast differentiation in the early stage.


Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis.

He M, Wang J, Wang G, Tian Y, Jiang L, Ren Z, Qiu C, Fu Q - Mol Med Rep (2016)

Effect of GC treatment on the mRNA expression of Runx2, osterix, osteocalcin and MMP-9, as measured by quantitative polymerase chain reaction. The mRNA expression levels of (A) MMP-9 increased, (B) of Runx2 remained the same and the expression levels of (C) osteocalcin and (D) osterix increased in the GC-treated group. The data are presented as the mean ± standard deviation (*P<0.05, vs. the control group). MMP, matrix metallopeptidase; GC, glucocorticoid; Runx2, runt-related transcription factor 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940104&req=5

f6-mmr-14-02-1054: Effect of GC treatment on the mRNA expression of Runx2, osterix, osteocalcin and MMP-9, as measured by quantitative polymerase chain reaction. The mRNA expression levels of (A) MMP-9 increased, (B) of Runx2 remained the same and the expression levels of (C) osteocalcin and (D) osterix increased in the GC-treated group. The data are presented as the mean ± standard deviation (*P<0.05, vs. the control group). MMP, matrix metallopeptidase; GC, glucocorticoid; Runx2, runt-related transcription factor 2.
Mentions: In order to identify the in-depth mechanism by which GCs regulate osteoclast differentiation, the mRNA expression levels of Runx2, osterix, osteocalcin and MMP-9 were determined. Runx2 is essential for osteoblastic differentiation and skeletal morphogenesis, and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. Osterix is a zinc finger-containing transcription factor expressed in osteoblasts that serves a role in the osteoblast differentiation pathway. It was suggested that Runx2 acts upstream of osterix, as previous studies demonstrated that in Runx2- mice, osterix is not expressed, whereas in osterix mice, Runx2 is expressed (19). As demonstrated in Fig. 6, the relative mRNA expression of Runx2 in the GC-treated group remained unchanged compared with the control group. In addition, the relative mRNA expression of osterix was increased in the GC-treated group compared with the control group (P<0.05; Fig. 6). The results indicated that GC treatment promoted osteoblast differentiation in the late stage, however had no effect on osteoblast differentiation in the early stage.

Bottom Line: The results demonstrated that the GC-treated group had a lower mean weight compared with the control group.In addition, tartarate‑resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group.The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

ABSTRACT
Osteonecrosis, also termed aseptic necrosis, is the cellular death of bone components due to interruption of the blood supply. Glucocorticoid (GC) therapy is a common non-traumatic cause of osteonecrosis. However, the mechanism by which GCs induce osteonecrosis remains to be elucidated. The aim of the present study was to investigate the effects of GCs on osteoclast and osteoblast differentiation and function in a GC‑induced osteonecrosis mouse model. BALB/c male mice (n=40; 4‑weeks‑old) were treated with dexamethasone and asparaginase for 8 weeks. The control group (n=20) was administered normal saline. The results demonstrated that the GC-treated group had a lower mean weight compared with the control group. Morphologically, 16/37 (43%) mice demonstrated significant osteonecrotic lesions in the GC‑treated group. However, osteonecrotic lesions were not observed in the mice of the control group. Furthermore, immunohistochemistry demonstrated that the GC‑treated group had a higher level of osteoprotegerin compared with the control group, without any change in the expression of receptor activator of nuclear factor‑κB ligand. In addition, tartarate‑resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group. Furthermore, the present study demonstrated that GCs increased expression levels of osterix and osteocalcin, and decreased expression of matrix metallopeptidase‑9 to regulate the differentiation and function of osteoblasts and osteoclasts. The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation. Therefore, regulating the differentiation and activity of the osteoclasts may be beneficial to the control and treatment of osteonecrosis.

No MeSH data available.


Related in: MedlinePlus