Ckip-1 in Osteoblasts Plays an Inhibition Role in Bone Formation in Aged Male Osteoporosis
Refereed conference paper presented and published in conference proceedings



摘要Introduction: Casein kinase-2 interacting protein-1 (Ckip-1) was newly identified as negative regulator of bone formation without activating bone resorption [1]. Pathologically, increased Ckip-1 mRNA expression associated with decreased osteocalcin mRNA expression was further observed within osteoblasts from aged osteoporotic men [2]. Thus, we hypothesized that Ckip-1 in osteoblasts could play an inhibition role in bone formation in aged male osteoporosis. In this study, we tested our hypothesis using the previously identifi ed cross-species Ckip-1 siRNA sequence [3] and the well developed osteoblast-specifi c delivery system [4]. Objectives: To examine the effect of the Ckip-1 siRNA encapsulated in (AspSerSer)6-liposome on trabecular bone mass, structure and bone formation in an aged gonad-intact male rat model, i.e. 16-month-old male SD rats.
Materials & Methods: 10 rats were firstly sacrificed before treatment as baseline (BS Group). Thereafter, 40 rats were given three periodic injections of Ckip-1 siRNA (siRNA Group) or non-sense siRNA (NC Group) (7.5 mg/kg) delivered by (AspSerSer)6-liposome or (AspSerSer)6-liposome alone (Veh Group) or PBS (CON group) at an interval of two weeks, respectively. All the rats were injected intraperitoneally with calcein green (10 mg/kg) and xylenol orange (30 mg/kg) 10 and 2 days before euthanasia, respectively. After sacrifi ce, the 5th vertebrae bodies (LV5) were dissected and subjected to microCT measurement and subsequent bone histomorphometric analysis.
Results: The microCT analysis data revealed that the BMD, BV/TV, Tb.Th and Tb.N in siRNA group were notably increased from baseline and all obviously higher in siRNA Group than those in NC, Veh and CON groups (Figure A). Consistently, a better organized trabecular micro-architecture was also found in siRNA Group compared to BS, NC, Veh and CON groups (Figure B). The bone histomorphometric analysis data showed that BFR, MAR and Ob.S/BS in siRNA Group were all signifi cantly increased from baseline and higher than those in NC, Veh and CON groups, whereas the Oc.S/BS was unchanged among all the groups (Figure C).
Conclusion: It indicated that Ckip-1 in osteoblasts could play an inhibition role in bone formation in aged male osteoporosis
著者Baosheng Guo, Jin Liu, Aiping Lu, Baoting Zhang, Ge Zhang.
會議名稱17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT)
會議地點Washington, DC
期刊名稱Molecular Therapy
會議論文集題名Molecular Therapy
頁次S39 - S40
Web of Science 學科類別Biotechnology & Applied Microbiology;Genetics & Heredity;Medicine, Research & Experimental;Biotechnology & Applied Microbiology;Genetics & Heredity;Research & Experimental Medicine

上次更新時間 2020-19-09 於 02:23