School of Chinese Medicine
The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment. Further, the reduced bone formation in GIO mice could not only be prevented by osteoblasts-specific Ckip-1 ablation, but also be attenuated after osteoblasts-specific Smad1 overexpression. Moreover, osteoblasts-targeting CKIP-1 siRNA treatment also attenuated the bone formation reduction in GIO mice. These study suggest that the highly expressed CKIP-1 in osteoblasts could suppress the Smad-dependent BMP signaling and contribute to the bone formation reduction in GIO. Targeting osteoblastic CKIP-1 would be a novel bone anabolic strategy for GIO patients.
Source Publication Title
Article number: 41295 (2017)
Nature Publishing Group
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This study was supported by the Ministry of Science and Technology of China (2013ZX09301307 to A.L.), (HKBU479111 to G.Z., HKBU478312 to G.Z., HKBU262913 to G.Z., HKBU261113 to A.L. CUHK14112915 to B.Z. and CUHK489213 to B.Z.), the Natural Science Foundation Council of China (81272045 to G.Z. 81272045 to B.G., 81401833 to B.G. and 81470072 to X.H.), the Research Grants Council & Natural Science Foundation Council of China (N_HKBU435/12 to G.Z.), the Croucher Foundation (Gnt#CAS14BU/CAS14201 to G.Z.), the Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/12-13/02 to A.L. and RC-IRMS/13-14/02 to G.Z.), the Hong Kong Baptist University Strategic Development Fund (SDF) (SDF13-1209-P01 to A.L.), the Hong Kong Research Grants Council (RGC) Early Career Scheme (ECS) (489213 to G.Z.), the Inter-institutional Collaborative Research Scheme of Hong Kong Baptist University (RC-ICRS/14-15/01 to G.Z.), the Faculty Research Grant of Hong Kong Baptist University (FRG1/13-14/024 to G.Z. FRG2/12-13/027 to G.Z. and FRG2/14-15/010 to G.Z.), the China Academy of Chinese Medical Sciences (Z0252 and Z0293 to A.L.). The statistical analysis was performed by a contract service from Bioinformedicine (http://www.bioinformedicine.com/index.php).
Link to Publisher's Edition
Liu, J., Lu, C., Wu, X., Zhang, Z., Li, J., Guo, B., Li, D., Liang, C., Dang, L., Pan, X., Peng, S., Lu, A., Zhang, B., & Zhang, G. (2017). Targeting osteoblastic casein kinase-2 interacting protein-1 to enhance Smad-dependent BMP signaling and reverse bone formation reduction in glucocorticoid-induced osteoporosis. Scientific Reports, 7, Article number: 41295 (2017). https://doi.org/10.1038/srep41295
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