Abstract
ABSTRACTPatients taking glucocorticoid or glucocorticoid-like drugs for an extended period of time may develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP). GIOP is the most common form of secondary osteoporosis, but the mechanism underlying its development is unclear. In the present study, we used prednisolone to treat zebrafish larvae to investigate GIOP. Our RNA deep-sequencing (RNA-seq) results show that prednisolone affects genes known to act in the extracellular region. Therefore the extracellular region, extracellular matrix, and collagen trimer might be involved in glucocorticoid-induced osteoporosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the focal adhesion signaling pathway is the most enriched signaling pathway in terms of differentially expressed genes (DEGs). In this pathway, integrin subunit alpha 10 (itga10) and integrin subunit beta like 1 (itgbl1), genes encoding two adapter proteins, were down-regulated in the prednisolone-treated larvae. Further experiments showed that prednisolone contributes to GIOP by down-regulating itga10 and itgbl1.
Highlights
Glucocorticoids (GCs) are a class of corticosteroids that bind to glucocorticoid receptors (GRs), which are present in almost every vertebrate cell to regulate metabolism (Kadmiel and Cidlowski, 2013)
Establishment of a zebrafish larva glucocorticoid-induced osteoporosis (GIOP) model induced by prednisolone For establishing the zebrafish larva GIOP model, 5 dpf larva zebrafish were exposed to 25 μM prednisolone and incubated with the drug until collected
The staining results showed that the area of stained bony tissue was decreased in the group exposed to 25 μM prednisolone compared with the Dimethyl Sulfoxide (DMSO) control groups (Fig. 1A-F)
Summary
Glucocorticoids (GCs) are a class of corticosteroids that bind to glucocorticoid receptors (GRs), which are present in almost every vertebrate cell to regulate metabolism (Kadmiel and Cidlowski, 2013). Clinical data show that 50% of patients taking GCs or GC-like drugs for 6 months or longer develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis (Adinoff and Hollister, 1983; Reid, 1997; Seibel et al, 2013). Another study revealed that apoptosis of osteoblasts induced by GCs is related to the activation of glycogen synthase kinase 3β (GSK 3β), which plays a role in the Wnt signaling pathway (Yun et al, 2009). The Wnt signaling pathway plays an important role in controlling osteoblast differentiation and bone formation (Qiang et al, 2009). In addition to the Wnt signaling pathway, the bone morphogenetic protein (BMP) pathway was shown to be affected by GCs resulting in inhibition of osteoblast differentiation (Boden et al, 1997). Several studies have focused on GIOP, the mechanism underlying its development is poorly understood
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