High dose glucocorticoid hampers bone formation and resorption after bone marrow ablation in rat.
We analyzed the effect of glucocorticoid on bone regeneration after bone marrow ablation in tibiae of 8-week-old rats. Methylprednisolone sodium succinate (MPSS) was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on days 1, 3, 5, 7, 10, 12, and 14 after ablation were subjected to tartrate-resistant acid phosphatase staining, immunohistochemistry, in situ hybridization, and transmission electron microscopy (TEM), and measurement of the volume of newly-formed bone and the osteoclast number. MPSS significantly decreased the newly-formed bone volume on day 7, and immature bone still remained on day 10 in the MPSS-treated group. The volume of this bone was significantly higher than that in the control group. However, there were no differences between the groups in the osteoclast number, the expression of mRNAs for osteoblast differentiation markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry. TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts in the MPSS-treated group had less developed ruffled borders, compared to those in the control group. These results suggest that MPSS treatment affects neither the differentiation nor the shape of osteoblasts, and does not change the osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both bone formation and resorption during bone regeneration after rat tibial bone marrow ablation, and inhibits ruffled border formation in osteoclasts. These data will be useful to develop bone regenerative therapies for bone diseases due to high dose steroid administration.
Kondo
Naoki
N
Division of Orthopaedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata 951-8510, Japan.
Tokunaga
Kunihiko
K
Ito
Tomoyuki
T
Arai
Katsumitsu
K
Amizuka
Norio
N
Minqi
Li
L
Kitahara
Hiroshi
H
Ito
Masayuki
M
Naito
Makoto
M
Shu-Ying
Jiang
J
Oda
Kimimitsu
K
Murai
Takehiro
T
Takano
Reiko
R
Ogose
Akira
A
Endo
Naoto
N
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001835:Body Weight; D001853:Bone Marrow / Q000601:surgery; D001861:Bone Regeneration / Q000187:drug effects*; D001862:Bone Resorption; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005819:Genetic Markers; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D010010:Osteoclasts / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000166:cytology / Q000254:growth & development / Q000601:surgery
D005819:Genetic Markers; D005938:Glucocorticoids; D012333:RNA, Messenger; D008776:Methylprednisolone Hemisuccinate; D000469:Alkaline Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat