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


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AbstractIntroduction: 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
All Author(s) ListBaosheng Guo, Jin Liu, Aiping Lu, Baoting Zhang, Ge Zhang.
Name of Conference17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT)
Start Date of Conference21/05/2014
End Date of Conference24/05/2014
Place of ConferenceWashington, DC
Country/Region of ConferenceUnited States of America
Journal nameMolecular Therapy
Proceedings TitleMolecular Therapy
Title of PublicationMOLECULAR THERAPY
Year2014
Volume Number22
Issue NumberS1
PublisherNATURE PUBLISHING GROUP
PagesS39 - S40
ISSN1525-0016
eISSN1525-0024
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiotechnology & Applied Microbiology;Genetics & Heredity;Medicine, Research & Experimental;Biotechnology & Applied Microbiology;Genetics & Heredity;Research & Experimental Medicine

Last updated on 2021-17-01 at 01:13