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Objective Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS. Methods Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells. Results The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value. Conclusion The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis. [ABSTRACT FROM AUTHOR]

Unloading-induced bone loss is a critical complication characterized by the imbalance of bone formation and resorption induced by long-term confinement in bed or spaceflight. CD31hiEmcnhi (type H) vessel is a specific subtype of capillary, which was coupled with osteogenesis. However, the change of type H vessel and its contributions to the unloading-induced bone loss remains undisclosed. Herein, we found that bone formation and the number of type H vessels were synchronously reduced in the hindlimb-unloading (HU) mice. Panax quinquefolium saponin (PQS) could increase bone mass, osteoblast function and the number of type H vessels in the HU mice. In vitro , PQS treatment accelerated HMECs migration, augmented the total tube loops and increased the secretion of VEGF and Noggin. Primary osteoblasts function was obviously increased when treated with supernatant from PQS-treated HMECs. These effects of PQS were substantially counteracted when VEGF and Noggin in HMECs were knocked down by siRNA. These results demonstrated that unloading-induced bone loss is coupled with reduction of type H vessels and PQS performs preventive function via promoting type H vessel angiogenesis, which is closely associated with endothelial cell-derived VEGF and Noggin. • Unloading induced bone loss is coupled with reduced numbers of type H vessel. • Panax quinquefolium saponin (PQS) facilitates type H vessel angiogenesis. • PQS protects from unloading induced bone loss. • HMEC derived VEGF and Noggin mediate the protective role of PQS in osteoblast. [ABSTRACT FROM AUTHOR]