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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 GCs treatment on the expression of RANKL. Cellular localization and protein expression of RANKL were measured using immunohistochemistry. No significant difference in RANKL expression was observed between the GC-treated and control groups. The data are presented as the mean ± standard deviation. GC, glucocorticoid; RNAKL, receptor activator of nuclear factor-κB ligand; intracellular optic density value of immunohistochemical staining.
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f4-mmr-14-02-1054: Effect of GCs treatment on the expression of RANKL. Cellular localization and protein expression of RANKL were measured using immunohistochemistry. No significant difference in RANKL expression was observed between the GC-treated and control groups. The data are presented as the mean ± standard deviation. GC, glucocorticoid; RNAKL, receptor activator of nuclear factor-κB ligand; intracellular optic density value of immunohistochemical staining.

Mentions: RANKL and OPG are essential for the regulation of various features of osteoclast functions, including proliferation, differentiation, fusion, activation and apoptosis (17). In particular, the balance between OPG and RANKL was demonstrated to modulate bone formation and resorption (18). Therefore, the cellular localization and protein expression of RANKL and OPG was assessed by immunohistochemistry. As demonstrated in Fig. 3, a lower positivity for OPG was observed in the control group compared with the higher OPG staining in the GC-treated group (P<0.05). No significant difference was indicated for the expression of RANKL between the GC-treated and the control groups (P>0.05; Fig. 4). These results indicated that the greater expression of OPG inhibited osteoclastogenesis following dexamethasone and asparaginase treatment.


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 GCs treatment on the expression of RANKL. Cellular localization and protein expression of RANKL were measured using immunohistochemistry. No significant difference in RANKL expression was observed between the GC-treated and control groups. The data are presented as the mean ± standard deviation. GC, glucocorticoid; RNAKL, receptor activator of nuclear factor-κB ligand; intracellular optic density value of immunohistochemical staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-14-02-1054: Effect of GCs treatment on the expression of RANKL. Cellular localization and protein expression of RANKL were measured using immunohistochemistry. No significant difference in RANKL expression was observed between the GC-treated and control groups. The data are presented as the mean ± standard deviation. GC, glucocorticoid; RNAKL, receptor activator of nuclear factor-κB ligand; intracellular optic density value of immunohistochemical staining.
Mentions: RANKL and OPG are essential for the regulation of various features of osteoclast functions, including proliferation, differentiation, fusion, activation and apoptosis (17). In particular, the balance between OPG and RANKL was demonstrated to modulate bone formation and resorption (18). Therefore, the cellular localization and protein expression of RANKL and OPG was assessed by immunohistochemistry. As demonstrated in Fig. 3, a lower positivity for OPG was observed in the control group compared with the higher OPG staining in the GC-treated group (P<0.05). No significant difference was indicated for the expression of RANKL between the GC-treated and the control groups (P>0.05; Fig. 4). These results indicated that the greater expression of OPG inhibited osteoclastogenesis following dexamethasone and asparaginase treatment.

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