Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis.
Nontraumatic osteonecrosis is related to alcohol and glucocorticoid with unknown pathogenesis. Increased adipogenesis decreases bone morphogenetic protein 2 (BMP2) gene expression after glucocorticoid treatment. Lovastatin enhances BMP2 gene expression in rodents, reverses the effects of glucocorticoids on bone, and prevents glucocorticoid-induced osteonecrosis in chickens and humans. We hypothesized patients with osteonecrosis are more susceptible to glucocorticoid treatment than patients without osteonecrosis. Marrow stromal cell cultures from 14 patients with osteonecrosis, and 10 patients without osteonecrosis were treated with dexamethasone (0.1 micromol/L), lovastatin (1 micromol/L), or combined treatment. BMP2 and osteocalcin gene expression were evaluated by reverse-transcriptase polymerase chain reaction and real-time polymerase chain reaction. The suppression of BMP2 by dexamethasone was more pronounced and the enhancement by lovastatin was less pronounced in the osteonecrosis group. Dexamethasone suppressed osteocalcin in the osteonecrosis group. Among the subgroups of osteonecrosis, suppression of BMP2 and osteocalcin by dexamethasone occurred in glucocorticoid-induced osteonecrosis group. Our data suggest individuals who are more susceptible to a glucocorticoid-induced decreases in BMP2 and osteocalcin gene expression are more likely to have osteonecrosis, especially glucocorticoid-induced osteonecrosis.
Chang
Je-Ken
JK
Department of Orthopedics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ho
Mei-Ling
ML
Yeh
Ching-Hua
CH
Chen
Chung-Hwan
CH
Wang
Gwo-Jaw
GJ
D000437:Alcoholism / Q000150:complications; D001854:Bone Marrow Cells / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005271:Femur Head Necrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D005938:Glucocorticoids; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003907:Dexamethasone; D008148:Lovastatin