Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis.
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.
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Ming
M
He
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Jiashi
J
Wang
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Guangbin
G
Wang
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Ye
Y
Tian
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Linlin
L
Jiang
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Zhaozhou
Z
Ren
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Chuang
C
Qiu
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Qin
Q
Fu
D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010020:Osteonecrosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D005938:Glucocorticoids; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D015675:Osteocalcin; D003907:Dexamethasone; D000071681:Tartrate-Resistant Acid Phosphatase; D020780:Matrix Metalloproteinase 9