Influence of glucocorticoids on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells

• Published in: BMC musculoskeletal disorders Vol. 15; no. 1; p. 239
• Main Authors: Zhou, Da-An, Zheng, Hong-Xin, Wang, Cheng-Wen, Shi, Dan, Li, Jian-Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.07.2014; BioMed Central
• Subjects: Alkaline Phosphatase - metabolism; Analysis; Animals; Biomarkers - metabolism; Bone marrow; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cell Cycle; Cell Differentiation; Cells, Cultured; Dexamethasone; Disease Models, Animal; Female; Genetic engineering; Glucocorticoids; Glucuronidase - genetics; Glucuronidase - metabolism; Male; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Osteogenesis; Osteoporosis - chemically induced; Osteoporosis - genetics; Osteoporosis - metabolism; Osteoporosis - pathology; Osteoprotegerin - metabolism; Phosphatases; Physiological aspects; RANK Ligand - metabolism; Rats, Sprague-Dawley; Rodents; Stem cells; China
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/1471-2474-15-239

Glucocorticoid has been used extensively in clinical applications, because of its several pharmacologic actions, which include immunosuppression, anti-inflammation, anti-shock, and relief of asthma. However, the long-term or high-dose application of glucocorticoid can induce adverse effects such as osteoporosis, which is known in this case as glucocorticoid-induced osteoporosis (GIOP). It is a secondary osteoporosis that results in easy fracturing, and even disability. Therefore it became a thorny issue. The rat model of glucocorticoid-induced osteoporosis (GIOP) was replicated to isolate BMSCs. Rats were assigned into four groups: normal, normal induction, GIOP, and GIOP induction. The growth cycle was monitored by using flow cytometry. Osteogenic differentiation was compared by using alkaline phosphatase (ALP) staining with a modified calcium cobalt method. The quantitative detection of osteoprotegerin and the receptor activator of nuclear factor kappa-B ligand (RANKL) was conducted by using enzyme-linked immunoassay. Finally, renal Klotho mRNA expression was assessed by using RT-PCR. BMSC proliferation was reduced in GIOP rats. The ALP-positive expression of normal BMSCs to the osteogenic induction solution was stronger than that of BMSCs from GIOP rats (P < 0.01). Osteoprotegerin expression was significantly higher in the normal induction group than in the normal, GIOP (P < 0.01), and GIOP induction groups (P < 0.05). RANKL expression was significantly higher in the normal induction group than in the other groups (P < 0.01) and significantly higher in the normal group than in the GIOP and GIOP induction groups (P < 0.01). RT-PCR analysis showed that renal Klotho mRNA expression was significantly reduced in the GIOP group compared with the normal group (P < 0.01). BMSC proliferation, osteogenic differentiation, and reactive activity to an osteogenic inductor were reduced in GIOP rats. Klotho mRNA expression decreased during GIOP induction.