2012
DOI: 10.1016/j.addr.2011.09.002
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RNA therapeutics targeting osteoclast-mediated excessive bone resorption

Abstract: RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare cr… Show more

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Cited by 36 publications
(18 citation statements)
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References 287 publications
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“…The NFATc1 is known as an essential factor for RANKL induced osteoclastogenesis [34] through regulating the expression of osteoclast-specific genes [92], including TRAF6, TRAP [89,93], calcitonin receptor [89,94] and cathepsin K [95]. In particular, the TRAP, a glycosylated monomeric metalloprotein enzyme, is highly expressed by osteoclasts and macrophages and serves as a major biochemical marker for osteoclast function [96], and the TRAP assay is a general tool for measurement of bone resorption and osteoclastogenesis [10,87,97]. In this study, the formation of TRAP-positive multinucleated osteoclasts significantly decreased by the siRNA(RANK)-MBG transfection (Fig.…”
Section: Discussionmentioning
confidence: 99%
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“…The NFATc1 is known as an essential factor for RANKL induced osteoclastogenesis [34] through regulating the expression of osteoclast-specific genes [92], including TRAF6, TRAP [89,93], calcitonin receptor [89,94] and cathepsin K [95]. In particular, the TRAP, a glycosylated monomeric metalloprotein enzyme, is highly expressed by osteoclasts and macrophages and serves as a major biochemical marker for osteoclast function [96], and the TRAP assay is a general tool for measurement of bone resorption and osteoclastogenesis [10,87,97]. In this study, the formation of TRAP-positive multinucleated osteoclasts significantly decreased by the siRNA(RANK)-MBG transfection (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, the recombinant human parathyroid hormone is an anabolic agent for bone formation and is approved only for the treatment of OP with high risk of fracture [5]. More recently, the use of monoclonal antibody for sclerostin or receptor activator of the nuclear factor kappa B ligand (RANKL), and the delivery of small interfering RNA (siRNA) have also been use for the treatment of OP [4,[9][10][11][12]. Furthermore, implantable biomaterials that incorporate drugs for targeting osteoclasts have been developed to treat OP [13,14].…”
Section: Introductionmentioning
confidence: 99%
“…Although the siRNA approach has been introduced to decrease bone resorption by downregulating the related gene expression of osteoclastogenesis, such as RANK, there is still little information about anabolic therapy in osteoporosis by siRNA strategy [72,73]. Theoretically, the negative regulator of osteogenic differentiation, osteoblast maturation and function could be the potential anabolic target by gene silencing for osteoporosis treatment.…”
Section: Sirna-mediated Gene Silencing Approach In Osteoporosis Treatmentioning
confidence: 99%
“…RNA interference (RNAi)-based approaches aimed at promoting osteo-blastic bone formation may hold therapeutic potential 1,2 . However, a major bottleneck for translating RNAi-based approaches into clinical application is the lack of osteoblast-specific osteogenic siRNA delivery systems 3 .…”
mentioning
confidence: 99%